Publications by authors named "Gaetano Santulli"

144 Publications

Targeting the phenotypic switch of vascular smooth muscle cells to tackle atherosclerosis.

Atherosclerosis 2021 May 28;324:117-120. Epub 2021 Mar 28.

Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York City, 10461, NY, United States; Department of Medicine (Division of Cardiology), Albert Einstein College of Medicine - Montefiore University Hospital, New York City, 10461, NY, United States; Department of Advanced Biomedical Sciences, "Federico II" University, Naples, 80131, Italy; International Translational Research and Medical Education (ITME), Naples, 80100, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.034DOI Listing
May 2021

Impact of thrombus aspiration in frail STEMI patients.

Aging Clin Exp Res 2021 Apr 4. Epub 2021 Apr 4.

University of Naples "Federico II", Naples, Italy.

Background: Despite primary percutaneous coronary intervention (PPCI) is generally considered the best therapy in older frail adults with ST-segment elevation myocardial infarction (STEMI), the incidence of re-hospitalization for cardiovascular diseases remains significant in these patients.

Aims: We hypothesized that thrombus aspiration (TA) before PPCI could be a useful treatment for reducing mortality and rehospitalizations in frail patients undergoing PPCI for STEMI.

Methods: We conducted a study comparing PPCI alone vs TA + PPCI in frail STEMI patients. We examined a cohort of consecutive frail patients aged ≥ 65 years with first STEMI treated with PPCI between February 2008 and July 2015 at the Department of Cardiology of the "Cardarelli" Hospital in Naples, Italy.

Results: The study was completed by 389 patients (PPCI: 195, TA + PPCI: 194). At 1-month follow-up, the rate of death from any cause was 7.0% in patients treated with PPCI alone vs 3.0% in patients treated with TA + PPCI (p 0.036), whereas death from cardiovascular causes was 6.0% in the PPCI group vs 3.0% in the TA + PPCI group (p 0.028). Equally important, the rate of re-hospitalization due to heart failure was 7.5% in the PPCI group vs 4.0% in TA + PPCI group (p 0.025) and the rate of re-hospitalization due to acute coronary syndrome was 10.0% in the PPCI group vs 4.5% in the TA + PPCI group (p 0.016).

Conclusion: These results indicate the importance of TA in the treatment of STEMI in a group of high-risk patients such as elderly with frailty.
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http://dx.doi.org/10.1007/s40520-021-01848-5DOI Listing
April 2021

Effects of Chronic Supplementation of L-Arginine on Physical Fitness in Water Polo Players.

Oxid Med Cell Longev 2021 15;2021:6684568. Epub 2021 Mar 15.

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

Background: Ergogenic nutritional supplementation is sought by professional athletes for improving physical performance; nevertheless, scientific evidence to support the chronic use of L-Arginine among water polo players is missing.

Methods: Seventeen male professional water polo players were randomly assigned to assume 5 grams per day of L-Arginine ( = 9) or placebo ( = 8) for 4 weeks. The players' fitness level was assessed in the maximal speed swimming test. Ear lobe blood samples taken before and after the effort for serum lactate content were analyzed. A speed-to-lactate ratio was generated at the baseline and after 4 weeks of treatment. We also tested the effects of L-Arginine , measuring NO production, mitochondrial respiration, and gene expression in human fibroblasts.

Results: L-Arginine did not modify BMI, muscle strength, and maximal speed at 200 meters after 4 weeks. However, L-Arginine ameliorated oxidative metabolism to exercise as suggested by the statistically significant lower lactate-to-speed ratio, which was not observed in placebo-treated controls. , L-Arginine induced the expression of a key regulator of mitochondrial biogenesis (PGC1) and genes encoding for complex I and increased the production of nitric oxide and the maximal oxygen consumption rate.

Conclusions: Chronic L-Arginine is safe and effective in ameliorating the oxidative metabolism of professional water polo players, through a mechanism of enhanced mitochondrial function.
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http://dx.doi.org/10.1155/2021/6684568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994081PMC
March 2021

Inclisiran: a new milestone on the PCSK9 road to tackle cardiovascular risk.

Eur Heart J Cardiovasc Pharmacother 2021 Feb 28. Epub 2021 Feb 28.

Department of Medicine, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, USA.

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http://dx.doi.org/10.1093/ehjcvp/pvab014DOI Listing
February 2021

miR-24 targets SARS-CoV-2 co-factor Neuropilin-1 in human brain microvascular endothelial cells: Insights for COVID-19 neurological manifestations.

Res Sq 2021 Feb 2. Epub 2021 Feb 2.

Albert Einstein College of Medicine.

Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an bloodâ€"brain barrier model.
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http://dx.doi.org/10.21203/rs.3.rs-192099/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872362PMC
February 2021

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells.

Noncoding RNA 2021 Feb 2;7(1). Epub 2021 Feb 2.

Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, USA.

Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood-brain barrier model.
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http://dx.doi.org/10.3390/ncrna7010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931075PMC
February 2021

Chronic kidney disease: Definition, updated epidemiology, staging, and mechanisms of increased cardiovascular risk.

J Clin Hypertens (Greenwich) 2021 Apr 17;23(4):831-834. Epub 2021 Jan 17.

Department of Medicine, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY, USA.

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http://dx.doi.org/10.1111/jch.14186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035205PMC
April 2021

In patients with early AF and CV conditions, early rhythm-control therapy vs. usual care reduced CV events at 5 years.

Authors:
Gaetano Santulli

Ann Intern Med 2021 01 5;174(1):JC6. Epub 2021 Jan 5.

Albert Einstein College of Medicine-Montefiore University Hospital New York, New York, USAUniversity of Naples 'Federico II' and ITME, Naples, Italy (G.S.).

Source Citation: Kirchhof P, Camm AJ, Goette A, et al. N Engl J Med. 2020;383:1305-16. 32865375.
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http://dx.doi.org/10.7326/ACPJ202101190-006DOI Listing
January 2021

What is linking COVID-19 and endothelial dysfunction? Updates on nanomedicine and bioengineering from the 2020 AHA Scientific Sessions.

Eur Heart J Cardiovasc Pharmacother 2020 Dec 30. Epub 2020 Dec 30.

Department of Medicine, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA.

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http://dx.doi.org/10.1093/ehjcvp/pvaa145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799225PMC
December 2020

Thyroid hormones regulate both cardiovascular and renal mechanisms underlying hypertension.

J Clin Hypertens (Greenwich) 2021 Feb 29;23(2):373-381. Epub 2020 Dec 29.

Department of Medicine, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY, USA.

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http://dx.doi.org/10.1111/jch.14152DOI Listing
February 2021

The discovery and development of IP3 receptor modulators: an update.

Expert Opin Drug Discov 2021 Jan 6:1-10. Epub 2021 Jan 6.

Department of Medicine (Division of Cardiology), Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, Montefiore University Hospital , New York City, USA.

: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular calcium (Ca) release channels located on the endoplasmic/sarcoplasmic reticulum. The availability of the structure of the ligand-binding domain of IP3Rs has enabled the design of compatible ligands, but the limiting step remains their actual effectiveness in a biological context. : This article summarizes the compelling literature on both agonists and antagonists targeting IP3Rs, emphasizing their strengths and limitations. The main challenges toward the discovery and development of IP3 receptor modulators are also described. : Despite significant progress in recent years, the pharmacology of IP3R still has major drawbacks, especially concerning the availability of specific antag onists. Moreover, drugs specifically targeting the three different subtypes of IP3R are especially needed.
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http://dx.doi.org/10.1080/17460441.2021.1858792DOI Listing
January 2021

Vitamin C and Cardiovascular Disease: An Update.

Antioxidants (Basel) 2020 Dec 3;9(12). Epub 2020 Dec 3.

Division of Cardiology, Department of Medicine, Institute of Aging Research, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Montefiore University Hospital, New York, NY 10461, USA.

The potential beneficial effects of the antioxidant properties of vitamin C have been investigated in a number of pathological conditions. In this review, we assess both clinical and preclinical studies evaluating the role of vitamin C in cardiac and vascular disorders, including coronary heart disease, heart failure, hypertension, and cerebrovascular diseases. Pitfalls and controversies in investigations on vitamin C and cardiovascular disorders are also discussed.
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http://dx.doi.org/10.3390/antiox9121227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761826PMC
December 2020

Exploiting GRK2 Inhibition as a Therapeutic Option in Experimental Cancer Treatment: Role of p53-Induced Mitochondrial Apoptosis.

Cancers (Basel) 2020 Nov 26;12(12). Epub 2020 Nov 26.

Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Napoli, Italy.

The involvement of GRK2 in cancer cell proliferation and its counter-regulation of p53 have been suggested in breast cancer even if the underlying mechanism has not yet been elucidated. Furthermore, the possibility to pharmacologically inhibit GRK2 to delay cancer cell proliferation has never been explored. We investigated this possibility by setting up a study that combined in vitro and in vivo models to underpin the crosstalk between GRK2 and p53. To reach this aim, we took advantage of the different expression of p53 in cell lines of thyroid cancer (BHT 101 expressing p53 and FRO cells, which are p53-null) in which we overexpressed or silenced GRK2. The pharmacological inhibition of GRK2 was achieved using the specific inhibitor KRX-C7. The in vivo study was performed in Balb/c nude mice, where we treated BHT-101 or FRO-derived tumors with KRX-C7. In our in vitro model, FRO cells were unaffected by GRK2 expression levels, whereas BHT-101 cells were sensitive, thus suggesting a role for p53. The regulation of p53 by GRK2 is due to phosphorylative events in Thr-55, which induce the degradation of p53. In BHT-101 cells, the pharmacologic inhibition of GRK2 by KRX-C7 increased p53 levels and activated apoptosis through the mitochondrial release of cytochrome c. These KRX-C7-mediated events were also confirmed in cancer allograft models in nude mice. In conclusion, our data showed that GRK2 counter-regulates p53 expression in cancer cells through a kinase-dependent activity. Our results further corroborate the anti-proliferative role of GRK2 inhibitors in p53-sensitive tumors and propose GRK2 as a therapeutic target in selected cancers.
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http://dx.doi.org/10.3390/cancers12123530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760517PMC
November 2020

miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19.

Biomedicines 2020 Oct 30;8(11). Epub 2020 Oct 30.

Department of Medicine, Wilf Family Cardiovascular Research Institute, Einstein-Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, USA.

The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Here, we focused on the study of microRNAs that specifically target TMPRSS2. Through a bioinformatic approach, we identified miR-98-5p as a suitable candidate. Since we and others have shown that endothelial cells play a pivotal role in the pathogenesis of the coronavirus disease 2019 (COVID-19), we mechanistically validated miR-98-5p as a regulator of TMPRSS2 transcription in two different human endothelial cell types, derived from the lung and from the umbilical vein. Taken together, our findings indicate that TMPRSS2 represents a valid target in COVID-19 treatment, which may be achieved by specific non-coding-RNA approaches.
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http://dx.doi.org/10.3390/biomedicines8110462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693865PMC
October 2020

Metabolic Flexibility of Mitochondria Plays a Key Role in Balancing Glucose and Fatty Acid Metabolism in the Diabetic Heart.

Diabetes 2020 10;69(10):2054-2057

Department of Medicine, Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY

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http://dx.doi.org/10.2337/dbi20-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506829PMC
October 2020

Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.

Hypertension 2020 11 8;76(5):1625-1636. Epub 2020 Sep 8.

Department of Medicine and Surgery (M.R., M.O., M.C.), University of Salerno, Italy.

Excessive BK (bradykinin) stimulation is responsible for the exaggerated permeabilization of the endothelium in angioedema. However, the molecular mechanisms underlying these responses have not been investigated. BK receptors are Gq-protein-coupled receptors phosphorylated by GRK2 (G protein-coupled receptor kinase 2) with a hitherto unknown biological and pathophysiological significance. In the present study, we sought to identify the functional role of GRK2 in angioedema through the regulation of BK signaling. We found that the accumulation of cytosolic Ca in endothelial cells induced by BK was sensitive to GRK2 activity, as it was significantly augmented by inhibiting the kinase. Accordingly, permeabilization and NO production induced by BK were enhanced, as well. In vivo, mice with reduced GRK2 levels in the endothelium (Tie2-CRE/GRK2) exhibited an increased response to BK in terms of vascular permeability and extravasation. Finally, patients with reduced GRK2 levels displayed a severe phenotype of angioedema. Taken together, these findings establish GRK2 as a novel pivotal regulator of BK signaling with an essential role in the pathophysiology of vascular permeability and angioedema.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544666PMC
November 2020

Genetics of adrenergic signaling drives coronary artery calcification.

Atherosclerosis 2020 10 17;310:88-90. Epub 2020 Aug 17.

Department of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine - Montefiore University Hospital, New York City, 10461, NY, United States; Department of Molecular Pharmacology, Albert Einstein College of Medicine - Montefiore University Hospital, New York City, 10461, NY, United States; Department of Advanced Biomedical Sciences, "Federico II" University, Naples, 80131, Italy; International Translational Research and Medical Education (ITME), Naples, 80100, Italy.

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http://dx.doi.org/10.1016/j.atherosclerosis.2020.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759099PMC
October 2020

Implications of ABO blood group in hypertensive patients with covid-19.

Res Sq 2020 Aug 12. Epub 2020 Aug 12.

Universita degli Studi della Campania Luigi Vanvitelli.

Hypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19. : In this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events. Patients in non-0 (n=92) vs. 0 blood group (n=72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p<0.05). Furthermore, patients in non-0 vs. 0 blood group had higher rate of cardiac injury (10 (13.9%) vs. 27 (29.3%)) and death, (6 (8.3%) vs. 18 (19.6%)), (p <0.05). At the multivariate analysis, Interleukin-6 (1.118, CI 95% 1.067-1.171) and non-0 blood group (2.574, CI 95% 1.207-5.490) were independent predictors of cardiac injury in hypertensive patients with covid-19. D-dimer (1.082, CI 95% 1.027-1.140), Interleukin-6 (1.216, CI 95% 1.082-1.367) and non-0 blood group (3.706, CI 95% 1.223-11.235) were independent predictors of deaths events in hypertensive patients with covid-19. : Taken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.
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http://dx.doi.org/10.21203/rs.3.rs-28258/v2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430579PMC
August 2020

Implications of AB0 blood group in hypertensive patients with covid-19.

BMC Cardiovasc Disord 2020 08 14;20(1):373. Epub 2020 Aug 14.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Hypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19.

Methods: In this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events.

Results: Patients in non-0 (n = 92) vs. 0 blood group (n = 72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p < 0.05). Furthermore, patients in non-0 vs. 0 blood group had higher rate of cardiac injury (10 (13.9%) vs. 27 (29.3%)) and death, (6 (8.3%) vs. 18 (19.6%)), (p < 0.05). At the multivariate analysis, Interleukin-6 (1.118, CI 95% 1.067-1.171) and non-0 blood group (2.574, CI 95% 1.207-5.490) were independent predictors of cardiac injury in hypertensive patients with covid-19. D-dimer (1.082, CI 95% 1.027-1.140), Interleukin-6 (1.216, CI 95% 1.082-1.367) and non-0 blood group (3.706, CI 95% 1.223-11.235) were independent predictors of deaths events in hypertensive patients with covid-19.

Conclusions: Taken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.
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http://dx.doi.org/10.1186/s12872-020-01658-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427694PMC
August 2020

Arginine and Endothelial Function.

Biomedicines 2020 Aug 6;8(8). Epub 2020 Aug 6.

Department of Neuroscience, "Federico II" University, 80131 Naples, Italy.

Arginine (L-arginine), is an amino acid involved in a number of biological processes, including the biosynthesis of proteins, host immune response, urea cycle, and nitric oxide production. In this systematic review, we focus on the functional role of arginine in the regulation of endothelial function and vascular tone. Both clinical and preclinical studies are examined, analyzing the effects of arginine supplementation in hypertension, ischemic heart disease, aging, peripheral artery disease, and diabetes mellitus.
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http://dx.doi.org/10.3390/biomedicines8080277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460461PMC
August 2020

A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy.

Nat Cancer 2020 Mar 2;1(3):315-328. Epub 2020 Mar 2.

Department of Medicine, Albert Einstein College of Medicine, Bronx NY, USA.

Doxorubicin remains an essential component of many cancer regimens, but its use is limited by lethal cardiomyopathy, which has been difficult to target, owing to pleiotropic mechanisms leading to apoptotic and necrotic cardiac cell death. Here we show that BAX is rate-limiting in doxorubicin-induced cardiomyopathy and identify a small-molecule BAX inhibitor that blocks both apoptosis and necrosis to prevent this syndrome. By allosterically inhibiting BAX conformational activation, this compound blocks BAX translocation to mitochondria, thereby abrogating both forms of cell death. When co-administered with doxorubicin, this BAX inhibitor prevents cardiomyopathy in zebrafish and mice. Notably, cardioprotection does not compromise the efficacy of doxorubicin in reducing leukemia or breast cancer burden in vivo, primarily due to increased priming of mitochondrial death mechanisms and higher BAX levels in cancer cells. This study identifies BAX as an actionable target for doxorubicin-induced cardiomyopathy and provides a prototype small-molecule therapeutic.
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http://dx.doi.org/10.1038/s43018-020-0039-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413180PMC
March 2020

miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting β-Arrestin 1.

Cells 2020 07 6;9(7). Epub 2020 Jul 6.

Department of Medicine, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY 10461, USA.

Glucagon-like peptide-1 (GLP-1) has been shown to potentiate glucose-stimulated insulin secretion binding GLP-1 receptor on pancreatic β cells. β-arrestin 1 (βARR1) is known to regulate the desensitization of GLP-1 receptor. Mounting evidence indicates that microRNAs (miRNAs, miRs) are fundamental in the regulation of β cell function and insulin release. However, the regulation of GLP-1/βARR1 pathways by miRs has never been explored. Our hypothesis is that specific miRs can modulate the GLP-1/βARR1 axis in β cells. To test this hypothesis, we applied a bioinformatic approach to detect miRs that could target βARR1; we identified hsa-miR-7-5p (miR-7) and we validated the specific interaction of this miR with βARR1. Then, we verified that GLP-1 was indeed able to regulate the transcription of miR-7 and βARR1, and that miR-7 significantly regulated GLP-1-induced insulin release and cyclic AMP (cAMP) production in β cells. Taken together, our findings indicate, for the first time, that miR-7 plays a functional role in the regulation of GLP-1-mediated insulin release by targeting βARR1. These results have a decisive clinical impact given the importance of drugs modulating GLP-1 signaling in the treatment of patients with type 2 diabetes mellitus.
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http://dx.doi.org/10.3390/cells9071621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407368PMC
July 2020

Cardiac BIN1 Replacement Therapy Ameliorates Inotropy and Lusitropy in Heart Failure by Regulating Calcium Handling.

JACC Basic Transl Sci 2020 Jun 22;5(6):579-581. Epub 2020 Jun 22.

Department of Medicine, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, New York.

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http://dx.doi.org/10.1016/j.jacbts.2020.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315227PMC
June 2020

Standardizing translational microbiome studies and metagenomic analyses.

Cardiovasc Res 2021 Feb;117(3):640-642

Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, Wilf Family Cardiovascular Research Institute, New York, NY, USA.

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http://dx.doi.org/10.1093/cvr/cvaa175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898946PMC
February 2021

No pleotropic effects of linagliptin on atherosclerotic plaques: Case closed.

Atherosclerosis 2020 07 28;305:61-63. Epub 2020 May 28.

Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, USA; Department of Molecular Pharmacology, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), The "Norman Fleischer" Institute for Diabetes and Metabolism (FIDAM), New York, NY, USA.

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http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535087PMC
July 2020

In acute HF, intensive and sustained vasodilation did not reduce a composite of death or HF readmission at 180 days.

Authors:
Gaetano Santulli

Ann Intern Med 2020 05;172(10):JC54

Albert Einstein College of Medicine-Montefiore University Hospital, New York, New York, USA, University of Naples 'Federico II' and ITME, Naples, Italy (G.S.).

Source Citation: Kozhuharov N, Goudev A, Flores D, et al. JAMA. 2019;322:2292-302. 31846016.
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http://dx.doi.org/10.7326/ACPJ202005190-054DOI Listing
May 2020

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence.

J Clin Med 2020 May 11;9(5). Epub 2020 May 11.

Department of Advanced Biomedical Sciences, International Translational Research and Medical Education Academic Research Unit (ITME), "Federico II" University, 80131 Naples, Italy.

The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.
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http://dx.doi.org/10.3390/jcm9051417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290769PMC
May 2020

Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update.

J Clin Med 2020 Apr 12;9(4). Epub 2020 Apr 12.

Department of Medicine, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, New York, NY 10461, USA.

Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.
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http://dx.doi.org/10.3390/jcm9041096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231134PMC
April 2020

Modulation of SERCA in Patients with Persistent Atrial Fibrillation Treated by Epicardial Thoracoscopic Ablation: The CAMAF Study.

J Clin Med 2020 Feb 17;9(2). Epub 2020 Feb 17.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Objectives: To evaluate atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF.

Background: Reduced levels of SERCA have been reported in the peripheral blood cells of patients with AF. We hypothesize that SERCA levels can predict the response to epicardial ablation.

Methods: We designed a prospective, multicenter, observational study to recruit, from October 2014 to June 2016, patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation.

Results: We enrolled 27 patients. Responders (n = 15) did not present AF recurrence after epicardial ablation at one-year follow-up; these patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type natriuretic peptide (BNP), and increased levels of SERCA compared to baseline and to nonresponders (p < 0.05). Furthermore, mean AF duration (Heart rate (HR) 1.235 (1.037-1.471), p < 0.05), Left atrium volume (LAV) (HR 1.755 (1.126-2.738), p < 0.05), BNP (HR 1.945 (1.895-1.999), p < 0.05), and SERCA (HR 1.763 (1.167-2.663), p < 0.05) were predictive of AF recurrence.

Conclusions: Our data indicate for the first time that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Therefore, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments.
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http://dx.doi.org/10.3390/jcm9020544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074346PMC
February 2020

Calcium supplements: Good for the bone, bad for the heart? A systematic updated appraisal.

Atherosclerosis 2020 03 29;296:68-73. Epub 2020 Jan 29.

Department of Medicine, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY, USA; International Translational Research and Medical Education Consortium (ITME), Naples, Italy.

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http://dx.doi.org/10.1016/j.atherosclerosis.2020.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276095PMC
March 2020