Publications by authors named "Sebastiano Sciarretta"

169 Publications

Impact of chronic use of heat-not-burn cigarettes on oxidative stress, endothelial dysfunction and platelet activation: the SUR-VAPES Chronic Study.

Thorax 2021 06 19;76(6):618-620. Epub 2021 Apr 19.

IRCCS NeuroMed, Pozzilli, Italy.

Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215900DOI Listing
June 2021

Differential Expression of Sphingolipid Metabolizing Enzymes in Spontaneously Hypertensive Rats: A Possible Substrate for Susceptibility to Brain and Kidney Damage.

Int J Mol Sci 2021 Apr 6;22(7). Epub 2021 Apr 6.

IRCCS Neuromed, Pozzilli 86077, Italy.

Alterations in the metabolism of sphingolipids, a class of biologically active molecules in cell membranes with direct effect on vascular homeostasis, are increasingly recognized as important determinant in different vascular disorders. However, it is not clear whether sphingolipids are implicated in the pathogenesis of hypertension-related cerebrovascular and renal damage. In this study, we evaluated the existence of possible abnormalities related to the sphingolipid metabolism in the brain and kidneys of two well validated spontaneously hypertensive rat strains, the stroke-prone (SHRSP) and the stroke-resistant (SHRSR) models, as compared to the normotensive Wistar Kyoto (WKY) rat strain. Our results showed a global alteration in the metabolism of sphingolipids in both cerebral and renal tissues of both hypertensive strains as compared to the normotensive rat. However, few defects, such as reduced expression of enzymes involved in the metabolism/catabolism of sphingosine-1-phosphate and in the de novo biosynthetic pathways, were exclusively detected in the SHRSP. Although further studies are necessary to fully understand the significance of these findings, they suggest that defects in specific lipid molecules and/or their related metabolic pathways may likely contribute to the pathogenesis of hypertensive target organ damage and may eventually serve as future therapeutic targets to reduce the vascular consequences of hypertension.
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http://dx.doi.org/10.3390/ijms22073796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038804PMC
April 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Editorial: Mitochondrial Dysfunction and Cardiovascular Diseases.

Front Cardiovasc Med 2021 22;8:645986. Epub 2021 Jan 22.

Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.

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http://dx.doi.org/10.3389/fcvm.2021.645986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874211PMC
January 2021

The complex network of mTOR signaling in the heart.

Cardiovasc Res 2021 Jan 29. Epub 2021 Jan 29.

Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA.

The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signaling revealed that mTORC1/2 elicit both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodeling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.
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http://dx.doi.org/10.1093/cvr/cvab033DOI Listing
January 2021

Beneficial effects of a combination of natural product activators of autophagy on endothelial cells and platelets.

Br J Pharmacol 2021 05 24;178(10):2146-2159. Epub 2021 Apr 24.

Department of Angio-Cardio-Neurology, IRCCS Neuromed, Località Camerelle, Pozzilli, Italy.

Background And Purpose: Oxidative stress and insufficient autophagy activity are associated with inflammatory processes and are common features of many cardiovascular diseases (CVDs). We investigated if a combination of natural activators of autophagy could modulate oxidative stress, platelet aggregation and endothelial cell survival and function in response to stress.

Experimental Approach: Ex vivo platelet aggregation and activation, H O production and autophagy were measured in platelets of subjects at high cardiovascular risk, including smokers, patients with metabolic syndrome (MetS) and patients with atrial fibrillation (AF). In vitro, the effects of a mixture of natural pro-autophagy molecules and antioxidants on platelets and human umbilical vein endothelial cells (HUVECs) were evaluated.

Key Result: Autophagy appeared to be inhibited, whereas aggregation was increased in platelets from AF and MetS patients and in smokers, as compared with healthy subjects. Treatment of platelets isolated from these patients with a mixture composed of trehalose, spermidine, catechin and epicatechin (Mix1) or with a mixture composed of trehalose, spermidine and nicotinamide (Mix2), significantly reduced platelet activation and oxidative stress, and increased autophagy, compared with the effect of each compound alone. Similarly, treatment of HUVECs with a combination of these compounds exhibited beneficial effects and increased endothelial cell survival, nitric oxide bioavailability and angiogenesis in response to stress in a potentiated manner.

Conclusion And Implications: A combination of natural activators of autophagy could inhibit platelet activity and oxidative stress and improve endothelial cell survival and function in a potentiated manner representing a useful strategy to reduce the effect of risk factors on CVD occurrence.

Linked Articles: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.
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http://dx.doi.org/10.1111/bph.15399DOI Listing
May 2021

The Role of Antioxidants Supplementation in Clinical Practice: Focus on Cardiovascular Risk Factors.

Antioxidants (Basel) 2021 Jan 20;10(2). Epub 2021 Jan 20.

Faculty of Medicine and Surgery, Sapienza University of Rome, 04100 Latina, Italy.

Oxidative stress may be defined as an imbalance between reactive oxygen species (ROS) and the antioxidant system to counteract or detoxify these potentially damaging molecules. This phenomenon is a common feature of many human disorders, such as cardiovascular disease. Many of the risk factors, including smoking, hypertension, hypercholesterolemia, diabetes, and obesity, are associated with an increased risk of developing cardiovascular disease, involving an elevated oxidative stress burden (either due to enhanced ROS production or decreased antioxidant protection). There are many therapeutic options to treat oxidative stress-associated cardiovascular diseases. Numerous studies have focused on the utility of antioxidant supplementation. However, whether antioxidant supplementation has any preventive and/or therapeutic value in cardiovascular pathology is still a matter of debate. In this review, we provide a detailed description of oxidative stress biomarkers in several cardiovascular risk factors. We also discuss the clinical implications of the supplementation with several classes of antioxidants, and their potential role for protecting against cardiovascular risk factors.
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http://dx.doi.org/10.3390/antiox10020146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909411PMC
January 2021

Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?

J Thromb Thrombolysis 2021 Jul 2;52(1):105-110. Epub 2021 Jan 2.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Patients with Coronavirus-associated disease-2019 (COVID-19) display alterations of the hemostatic system and the presence of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet activity, aggregation and agglutination still needs to be clarified. We measured total levels of von Willebrand factor (vWF) and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the intensive care unit of our Institution. Moreover, we evaluated platelet aggregation in response to agonists (ADP, collagen, arachidonic acid) and platelet agglutination in response to ristocetin. We found that levels of vWF antigen and the active form of vWF binding to platelets (vWF:RCo), were markedly increased in these patients. These results were associated with higher agglutination rates induced by ristocetin, thereby indirectly indicating an increased capability of vWF to bind to platelets. Conversely, we found that platelet aggregation in response to both ADP and collagen was lower in COVID-19 patients compared to healthy volunteers. This study shows that COVID-19 is associated with increased vWF-induced platelet agglutination but reduced platelet responsivity to aggregation stimuli. Our findings have translational relevance since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic strategies in COVID-19 patients.
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http://dx.doi.org/10.1007/s11239-020-02339-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778414PMC
July 2021

YAP plays a crucial role in the development of cardiomyopathy in lysosomal storage diseases.

J Clin Invest 2021 Mar;131(5)

Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey, USA.

Lysosomal dysfunction caused by mutations in lysosomal genes results in lysosomal storage disorder (LSD), characterized by accumulation of damaged proteins and organelles in cells and functional abnormalities in major organs, including the heart, skeletal muscle, and liver. In LSD, autophagy is inhibited at the lysosomal degradation step and accumulation of autophagosomes is observed. Enlargement of the left ventricle (LV) and contractile dysfunction were observed in RagA/B cardiac-specific KO (cKO) mice, a mouse model of LSD in which lysosomal acidification is impaired irreversibly. YAP, a downstream effector of the Hippo pathway, was accumulated in RagA/B cKO mouse hearts. Inhibition of YAP ameliorated cardiac hypertrophy and contractile dysfunction and attenuated accumulation of autophagosomes without affecting lysosomal function, suggesting that YAP plays an important role in mediating cardiomyopathy in RagA/B cKO mice. Cardiomyopathy was also alleviated by downregulation of Atg7, an intervention to inhibit autophagy, whereas it was exacerbated by stimulation of autophagy. YAP physically interacted with transcription factor EB (TFEB), a master transcription factor that controls autophagic and lysosomal gene expression, thereby facilitating accumulation of autophagosomes without degradation. These results indicate that accumulation of YAP in the presence of LSD promotes cardiomyopathy by stimulating accumulation of autophagosomes through activation of TFEB.
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http://dx.doi.org/10.1172/JCI143173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919732PMC
March 2021

Inhibition of miR-155 Attenuates Detrimental Vascular Effects of Tobacco Cigarette Smoking.

J Am Heart Assoc 2020 12 2;9(24):e017000. Epub 2020 Dec 2.

Department of Medical-Surgical Sciences and Biotechnologies Sapienza University of Rome Latina Italy.

Background The role of microRNAs dysregulation in tobacco cigarette smoking-induced vascular damage still needs to be clarified. We assessed the acute effects of tobacco cigarette smoking on endothelial cell-related circulating microRNAs in healthy subjects. In addition, we investigated the potential role of microRNAs in smoking-dependent endothelial cell damage. Methods and Results A panel of endothelial-related microRNAs was quantified in healthy subjects before and after smoking 1 tobacco cigarette. Serum levels of miR-155 were found to be significantly increased shortly after smoking. We also observed a progressive and significant miR-155 accumulation in culture media of human endothelial cells after 30 minutes and up to 4 hours of cigarette smoke condensate treatment in vitro without evidence of cell death, indicating that miR-155 can be released by endothelial cells in response to smoking stress. Cigarette smoke condensate appeared to enhance oxidative stress and impair cell survival, angiogenesis, and NO metabolism in human endothelial cells. Notably, these effects were abrogated by miR-155 inhibition. We also observed that miR-155 inhibition rescued the deleterious effects of cigarette smoke condensate on endothelial-mediated vascular relaxation and oxidative stress in isolated mouse mesenteric arteries. Finally, we found that exogenous miR-155 overexpression mimics the effects of smoking stress by inducing the upregulation of inflammatory markers, impairing angiogenesis and reducing cell survival. These deleterious effects were associated with downregulation of vascular endothelial growth factor and endothelial NO synthetase. Conclusions Our results suggest that miR-155 dysregulation may contribute to the deleterious vascular effects of tobacco smoking.
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http://dx.doi.org/10.1161/JAHA.120.017000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955400PMC
December 2020

Renal arteries denervation with second generation systems: a remedy for resistant hypertension?

Eur Heart J Suppl 2020 Nov 18;22(Suppl L):L160-L165. Epub 2020 Nov 18.

Department of Cardiology, Santa Maria Goretti Hospital, Latina, Italy.

Initial studies on renal denervation (RDN) for the treatment of non-controlled arterial hypertension (HTN) through radiofrequency ablation of renal arteries demonstrated that RDN is an effective therapeutic strategy to reduce arterial blood pressure (BP). Nonetheless, the first randomized study, SYMPLICITY-HTN-3, failed to demonstrate a clear benefit for RND over the control group. Technologic evolution, with the introduction of new second generation multi-electrode devices, allowed deep energy delivery along the full circumference of the vessel. Two recent randomized studies involving patients assuming (SPYRAL HTN-ON MED) or not (SPYRAL HTN-OFF MED) antihypertensive pharmacologic treatment, demonstrated the efficacy and safety of RDN using second generation systems for radiofrequency ablation. Another recent randomized study demonstrated that RDN with ultrasounds (RADIANCE-HTN SOLO) of the main renal arteries led to a significant BP reduction compared to the control group. These studies have once again raised the interest of the scientific community towards attempting to define the appropriate role of RDN in the treatment of hypertension. Nonetheless, larger and longer clinical trials will be necessary to draw further conclusions.
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http://dx.doi.org/10.1093/eurheartj/suaa158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673618PMC
November 2020

A Novel Promising Frontier for Human Health: The Beneficial Effects of Nutraceuticals in Cardiovascular Diseases.

Int J Mol Sci 2020 Nov 18;21(22). Epub 2020 Nov 18.

Department of Angio-Cardio-Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy.

Cardiovascular diseases (CVDs) such as hypertension, atherosclerosis, myocardial infarction, and diabetes are a significant public health problem worldwide. Although several novel pharmacological treatments to reduce the progression of CVDs have been discovered during the last 20 years, the better way to contain the onset of CVDs remains prevention. In this regard, nutraceuticals seem to own a great potential in maintaining human health, exerting important protective cardiovascular effects. In the last years, there has been increased focus on identifying natural compounds with cardiovascular health-promoting effects and also to characterize the molecular mechanisms involved. Although many review articles have focused on the individual natural compound impact on cardiovascular diseases, the aim of this manuscript was to examine the role of the most studied nutraceuticals, such as resveratrol, cocoa, quercetin, curcumin, brassica, berberine and Spirulina platensis, on different CVDs.
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http://dx.doi.org/10.3390/ijms21228706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698807PMC
November 2020

Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study.

Oxid Med Cell Longev 2020 27;2020:4165358. Epub 2020 Oct 27.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls.

Methods And Results: Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( = 10, age 67.8 ± 3.2, male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, < 0.001), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, < 0.001), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, < 0.001), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, < 0.001). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed.

Conclusions: Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.
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http://dx.doi.org/10.1155/2020/4165358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641261PMC
May 2021

Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis.

Antioxidants (Basel) 2020 Nov 10;9(11). Epub 2020 Nov 10.

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated the ongoing coronavirus disease-2019 (COVID-19) pandemic, still with an uncertain outcome. Besides pneumonia and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), other features became evident in the context of COVID-19. These includes endothelial and coagulation dysfunction with disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS), along with the occurrence of neurological alterations. The multi-system nature of such viral infection is a witness to the exploitation and impairment of ubiquitous subcellular and metabolic pathways for the sake of its life-cycle, ranging from host cell invasion, replication, transmission, up to a cytopathic effect and overt systemic inflammation. In this frame, alterations in cell-clearing systems of the host are emerging as a hallmark in the pathogenesis of various respiratory viruses, including SARS-CoV-2. Indeed, exploitation of the autophagy and proteasome pathways might contribute not only to the replication of the virus at the site of infection but also to the spreading of either mature virions or inflammatory mediators at both cellular and multisystem levels. In this frame, besides a pharmacological therapy, many researchers are wondering if some non-pharmacological substances might counteract or positively modulate the course of the infection. The pharmacological properties of natural compounds have gained increasing attention in the field of alternative and adjunct therapeutic approaches to several diseases. In particular, several naturally-occurring herbal compounds (mostly polyphenols) are reported to produce widespread antiviral, anti-inflammatory, and anti-oxidant effects while acting as autophagy and (immuno)-proteasome modulators. This article attempts to bridge the perturbation of autophagy and proteasome pathways with the potentially beneficial effects of specific phytochemicals and flavonoids in viral infections, with a focus on the multisystem SARS-CoV-2 infection.
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http://dx.doi.org/10.3390/antiox9111105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697279PMC
November 2020

Caloric restriction mimetics for the treatment of cardiovascular diseases.

Cardiovasc Res 2021 May;117(6):1434-1449

Centre de Recherche des Cordeliers, Team "Metabolism, Cancer & Immunity", INSERM UMRS1138, Université de Paris, Sorbonne Université, 75006 Paris, France.

Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis, or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodelling in animal models of ageing, mechanical overload, chronic myocardial ischaemia, and in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischaemia-reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.
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http://dx.doi.org/10.1093/cvr/cvaa297DOI Listing
May 2021

How to implement research studies on extracellular vesicle administration in myocardial infarction?

Trends Cardiovasc Med 2020 Sep 22. Epub 2020 Sep 22.

Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Avenue, G-609, Newark, NJ, United States. Electronic address:

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http://dx.doi.org/10.1016/j.tcm.2020.09.003DOI Listing
September 2020

T2238C atrial natriuretic peptide gene variant and cardiovascular events in patients with atrial fibrillation: A substudy from the ATHERO-AF cohort.

Int J Cardiol 2021 01 28;322:245-249. Epub 2020 Aug 28.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, Latina 40100, Italy; IRCCS Neuromed, Località Camerelle, Pozzilli, (IS), 86077, Italy; This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Background: The T2238C variant of the atrial natriuretic peptide (ANP) gene has emerged as a novel risk factor for the incidence of cardiovascular events. However, the impact of this variant on cardiovascular outcome in patients with atrial fibrillation (AF) is unknown.

Methods: We included 557 anticoagulated patients with non-valvular AF randomly selected from the prospective ATHERO-AF cohort. Patients underwent genetic analysis for the T2238C/ANP variant and were grouped as wild type or heterozygous or homozygous for C2238 variant allele. Primary endpoint was a composite of cardiovascular events (CVEs) including cardiovascular death, fatal/non-fatal ischemic stroke and myocardial infarction. Overall, 429 patients carried the TT wild type genotype, 110 patients (19.7%) were heterozygous (T/C) and 18 patients (3.2%) were homozygous (CC).

Results: Incidence of CVEs was higher in homozygous patients for C2238 allele at unadjusted analysis (log-rank test, p = 0.042 for additive model, p = 0.043 for recessive model). The multivariable Cox proportional hazards regression analysis confirmed that C2238 ANP allele was associated with CVEs in the additive (p = 0.008) and recessive models (p = 0.005).

Conclusions: Carrier status for the C2238/ANP variant allele is associated with an increased risk of CVEs in anticoagulated AF patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.077DOI Listing
January 2021

Comparative Indoor Pollution from Glo, Iqos, and Juul, Using Traditional Combustion Cigarettes as Benchmark: Evidence from the Randomized SUR-VAPES AIR Trial.

Int J Environ Res Public Health 2020 08 19;17(17). Epub 2020 Aug 19.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy.

Modified risk products (MRP) such as electronic vaping cigarettes (EVC) and heat-not-burn cigarettes (HNBC) are appealing alternatives to combustion cigarettes. Limited between- and within-device comparative data are available on MRP. We aimed at comparing indoor particulate matter (PM) emissions measured in a randomized trial enforcing standardized smoking sessions, testing different devices and flavors of MRP, using traditional combustion cigarettes (TCC) as benchmark. Overall, MRP yielded significantly lower levels of indoor PM in comparison to TCC (with median PM levels during smoking for MRP < 100 μg/m, and for TCC > 1000 μg/m). Despite this, significant differences among MRP were found, with Iqos appearing associated with a significantly lower burden of emissions for all the monitored fractions of PM, including total PM (all < 0.05). Precisely, during use, PM ≤1 µm (PM) emissions were 28 (16; 28) μg/m for Glo, 25 (15; 57) μg/m for Iqos, and 73 (15; 559) μg/m for Juul ( < 0.001 for Glo vs. Iqos, < 0.001 for Glo vs. Juul, and = 0.045 for Iqos vs. Juul). Exploratory within-MRP analyses suggested significant differences between flavors, favoring, for instance, Ultramarine for Glo, Bronze for Iqos, and Mango for Juul, even if results varied substantially according to individual smoker. In conclusion, leading MRP have significantly less intense and persistent effects on indoor pollution in comparison to TCC. Yet, when focusing solely on MRP, between-product and between-flavor differences appear, with quantitative estimates suggesting lower polluting effects with Iqos. These results, if confirmed externally, could be used to individualize product and flavor choice to minimize the untoward effects of EVC and HNBC on indoor pollution.
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http://dx.doi.org/10.3390/ijerph17176029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504617PMC
August 2020

Epigenetic Remodeling in Obesity-Related Vascular Disease.

Antioxid Redox Signal 2021 05 9;34(15):1165-1199. Epub 2020 Sep 9.

Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland.

The prevalence of obesity and cardiometabolic phenotypes is alarmingly increasing across the globe and is associated with atherosclerotic vascular complications and high mortality. In spite of multifactorial interventions, vascular residual risk remains high in this patient population, suggesting the need for breakthrough therapies. The mechanisms underpinning obesity-related vascular disease remain elusive and represent an intense area of investigation. Epigenetic modifications-defined as environmentally induced chemical changes of DNA and histones that do not affect DNA sequence-are emerging as a potent modulator of gene transcription in the vasculature and might significantly contribute to the development of obesity-induced endothelial dysfunction. DNA methylation and histone post-translational modifications cooperate to build complex epigenetic signals, altering transcriptional networks that are implicated in redox homeostasis, mitochondrial function, vascular inflammation, and perivascular fat homeostasis in patients with cardiometabolic disturbances. Deciphering the epigenetic landscape in the vasculature is extremely challenging due to the complexity of epigenetic signals and their function in regulating transcription. An overview of the most important epigenetic pathways is required to identify potential molecular targets to treat or prevent obesity-related endothelial dysfunction and atherosclerotic disease. This would enable the employment of precision medicine approaches in this setting. Current and future research efforts in this field entail a better definition of the vascular epigenome in obese patients as well as the unveiling of novel, cell-specific chromatin-modifying drugs that are able to erase specific epigenetic signals that are responsible for maladaptive transcriptional alterations and vascular dysfunction in obese patients. . 34, 1165-1199.
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http://dx.doi.org/10.1089/ars.2020.8040DOI Listing
May 2021

A novel signalling mechanism regulating telomere length in cardiomyocytes.

Cardiovasc Res 2021 01;117(1):13-14

Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina 04100, Italy.

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http://dx.doi.org/10.1093/cvr/cvaa210DOI Listing
January 2021

Tackling myocardial oxidative stress with empagliflozin: are we big enough to fight heart failure with preserved ejection fraction?

Cardiovasc Res 2021 01;117(2):343-345

Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, Schlieren, CH-8952, Switzerland.

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http://dx.doi.org/10.1093/cvr/cvaa196DOI Listing
January 2021

Electronic cigarette.

Eur Heart J Suppl 2020 Jun 23;22(Suppl E):E25-E29. Epub 2020 Mar 23.

Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche, Sapienza Università di Roma.

Despite significant efforts during the last decades, cigarette smoking still remains prevalent. Discouraging the use of all tobacco products, it is certainly the most effective mean to enhance public health, but complete prohibition is unlikely to succeed. The greatest challenge is the approach to chronic smokers, particularly those affected with cardiovascular conditions. To better support these patients during the difficult process leading to complete smoke cessation, it is important to characterize each patient from a clinical and psychological perspective, introducing the most reliable approaches to incentivize and support abstinence, such as varenicline and nicotine replacement therapy, thus providing a personalized recommendation. The recent introduction of electronic systems for nicotine release or tobacco heating (electronic cigarettes), offers an important challenge. These devices are reasonably considered as tools, thus providing a useful alternative which unable the patient a smoother transition toward smoking cessation, also presenting an array of choices among which a personalized selection could be made. This technology, though, should not be overemphasized, considering also its potential harmful effects, and certainly its use should be strongly discouraged in non-smokers, particularly at young age. This approach, cautious and pragmatic, aside from demonization or over-enthusiastic appraisal, could provide favourable results in the constant struggle against cigarette smoking.
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http://dx.doi.org/10.1093/eurheartj/suaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270959PMC
June 2020

A randomized trial comparing the acute coronary, systemic, and environmental effects of electronic vaping cigarettes versus heat-not-burn cigarettes in smokers of combustible cigarettes undergoing invasive coronary assessment: rationale and design of the SUR-VAPES 3 trial.

Minerva Cardioangiol 2020 Dec 2;68(6):548-555. Epub 2020 Jun 2.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.

Background: Traditional combustible cigarette (TCC) smoking remains a major cause of preventable cardiovascular morbidity and mortality. Modified risk products (MRP) such as electronic vaping cigarettes (EVC) and heat-not-burn cigarettes (HNBC) may be safer than TCC but may still have detrimental oxidative, platelet and vascular effects of particular importance to people with symptomatic coronary artery disease (CAD).

Methods: We aimed to compare the acute coronary, systemic and environmental effects of two leading MRP in 20 TCC smokers admitted for invasive coronary assessment of CAD and willing to quit or after prior failed quitting attempts. After confirmation at angiography of an intermediate coronary stenosis, coronary flow reserve (CFR) will be appraised. Patients will then be randomized 1:1 to use a single EVC or a single HNBC in the catheterization laboratory, followed by repeat CFR measurement. The primary endpoint will be the change in CFR before and after product use. Quantitative coronary angiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) will also be measured.

Results: We expected to accrue results able to: 1) test whether MRP have in general a detrimental impact on coronary vascular function in TCC smokers; 2) test whether EVC have a different impact than HNBC on coronary function; 3) provide ancillary pathophysiologic and translational insights on the acute risk and safety profile of MRP in TCC smokers with established cardiovascular disease, including complex correlations between coronary, cardiac, systemic and environmental effects. In addition, by directly informing participants of their individual results, they will be further empowered to quit TCC.

Conclusions: The Sapienza University of Rome-Vascular Assessment of Proatherosclerotic Effects of Smoking (SUR-VAPES) 3 trial will provide important insights into the pathophysiologic cardiovascular impact of EVC and HNBC, also suitable to inform patients and individualize their smoking cessation strategy.
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http://dx.doi.org/10.23736/S0026-4725.20.05181-6DOI Listing
December 2020

Impact of environmental pollution and weather changes on the incidence of ST-elevation myocardial infarction.

Eur J Prev Cardiol 2020 Jun 2:2047487320928450. Epub 2020 Jun 2.

Division of Cardiology, Santa Maria Goretti Hospital, Italy.

Background: Environmental pollution and weather changes unfavorably impact on cardiovascular disease. However, limited research has focused on ST-elevation myocardial infarction (STEMI), the most severe yet distinctive form of acute coronary syndrome.

Methods And Results: We appraised the impact of environmental and weather changes on the incidence of STEMI, analysing the bivariate and multivariable association between several environmental and atmospheric parameters and the daily incidence of STEMI in two large Italian urban areas. Specifically, we appraised: carbon monoxide (CO), nitrogen dioxide (NO2), nitric oxide (NOX), ozone, particulate matter smaller than 10 μm (PM10) and than 2.5 μm (PM2.5), temperature, atmospheric pressure, humidity and rainfall. A total of 4285 days at risk were appraised, with 3473 cases of STEMI. Specifically, no STEMI occurred in 1920 (44.8%) days, whereas one or more occurred in the remaining 2365 (55.2%) days. Multilevel modelling identified several pollution and weather predictors of STEMI. In particular, concentrations of CO (=0.024), NOX (=0.039), ozone (=0.003), PM10 (=0.033) and PM2.5 (=0.042) predicted STEMI as early as three days before the event, as well as subsequently, and NO predicted STEMI one day before ( = 0.010), as well as on the same day. A similar predictive role was evident for temperature and atmospheric pressure (all  < 0.05).

Conclusions: The risk of STEMI is strongly associated with pollution and weather features. While causation cannot yet be proven, environmental and weather changes could be exploited to predict STEMI risk in the following days.
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http://dx.doi.org/10.1177/2047487320928450DOI Listing
June 2020

An overview of cycling as active transportation and as benefit for health.

Minerva Cardioangiol 2020 Apr;68(2):81-97

Mediterranea Cardiocentro, Naples, Italy -

Active transportation is defined as travelling on foot, by bicycle or other non-motorized means, sometimes in combination with other forms of public transportation, in contrast with the use of motor vehicles. The prevalence of sedentary lifestyle and physical inactivity is a growing epidemic in most developed countries that spread over the last three decades; active transportation may be a promising approach to increase physical activity and reduce the risk of non-communicable diseases improving cardiorespiratory fitness and cardiometabolic health. The health benefits of physical activity in reducing mortality and morbidity have been proved by several publications. Cardiorespiratory fitness can be improved by regular physical activity with an amelioration of insulin sensitivity, blood lipid profile, body composition, inflammation, and blood pressure. Active transportation as a daily physical activity is less expensive compared to motor vehicle use. The advantages are remarkable in terms of contrasting obesity and sedentary lifestyle, decrease motor traffic congestion and mitigate climate change. Massive investments in policies and interventions aimed to increase active transportation are not generally promoted and there are differences in the prevalence of active transportation in the daily routine among different areas. As in the literature several studies as randomized trials or observational studies have been published, with different end-points, in order to investigate if active commuting may be the right answer to improve cardiorespiratory fitness and cardiometabolic health, we aimed to review the available evidences of cycling as an active transportation and to consider its benefits on health.
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http://dx.doi.org/10.23736/S0026-4725.20.05182-8DOI Listing
April 2020

The role of mitochondrial dynamics in cardiovascular diseases.

Br J Pharmacol 2021 05 19;178(10):2060-2076. Epub 2020 May 19.

Department of AngioCardioNeurology, IRCCS Neuromed, Pozzili, Italy.

The process of mitochondrial dynamics is emerging as a core player in cardiovascular homeostasis. This process refers to the co-ordinated cycles of biogenesis, fusion, fission and degradation to which mitochondria constantly undergo to maintain their integrity, distribution and size. These mechanisms represent an early response to mitochondrial stress, confining organelle portions that are irreversibly damaged and preserving mitochondrial function. Accumulating evidence demonstrates that impairment in mitochondrial dynamics leads to myocardial damage and cardiac disease progression in a variety of disease models, including pressure overload, ischaemia/reperfusion and metabolic disturbance. These findings suggest that modulation of mitochondrial dynamics may be considered as a valid therapeutic strategy in cardiovascular diseases. In this review, we discuss the current evidence about the role of mitochondrial dynamics in cardiac pathophysiology, with a particular focus on the mechanisms underlying the development of cardiac hypertrophy and heart failure, metabolic and genetic cardiomyopathies, ischaemia/reperfusion injury, atherosclerosis and ischaemic stroke. LINKED ARTICLES: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.
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http://dx.doi.org/10.1111/bph.15068DOI Listing
May 2021

SARS-CoV-2 and COVID-19: facing the pandemic together as citizens and cardiovascular practitioners.

Minerva Cardioangiol 2020 04 9;68(2):61-64. Epub 2020 Mar 9.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.

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http://dx.doi.org/10.23736/S0026-4725.20.05250-0DOI Listing
April 2020

Air pollution, climate changes and cardiovascular diseases: a nightmare threesome!

Minerva Cardioangiol 2020 Aug 26;68(4):282-284. Epub 2020 Feb 26.

Division of Cardiology, S. Maria Goretti Hospital, Latina, Italy -

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http://dx.doi.org/10.23736/S0026-4725.20.05122-1DOI Listing
August 2020

Novel Basic Science Insights to Improve the Management of Heart Failure: Review of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology.

Int J Mol Sci 2020 Feb 11;21(4). Epub 2020 Feb 11.

Department of Advanced Biomedical Sciences, Federico II University, 80131 Naples, Italy.

Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.
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http://dx.doi.org/10.3390/ijms21041192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072832PMC
February 2020
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