Publications by authors named "Lidia Sada"

6 Publications

  • Page 1 of 1

Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients.

J Cardiovasc Med (Hagerstown) 2019 Nov;20(11):771-779

Department of Translational and Precision Medicine.

Aims: Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients.

Methods: Seventy patients were enrolled (64 women and six men; mean age 56.7 ± 14 years) with a disease duration of 11.1 ± 8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses.

Results: Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development.

Conclusion: Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.
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http://dx.doi.org/10.2459/JCM.0000000000000852DOI Listing
November 2019

Obesity-induced activation of JunD promotes myocardial lipid accumulation and metabolic cardiomyopathy.

Eur Heart J 2019 03;40(12):997-1008

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

Aims: Metabolic cardiomyopathy (MC)-characterized by intra-myocardial triglyceride (TG) accumulation and lipotoxic damage-is an emerging cause of heart failure in obese patients. Yet, its mechanisms remain poorly understood. The Activator Protein 1 (AP-1) member JunD was recently identified as a key modulator of hepatic lipid metabolism in obese mice. The present study investigates the role of JunD in obesity-induced MC.

Methods And Results: JunD transcriptional activity was increased in hearts from diet-induced obese (DIO) mice and was associated with myocardial TG accumulation and left ventricular (LV) dysfunction. Obese mice lacking JunD were protected against MC. In DIO hearts, JunD directly binds PPARγ promoter thus enabling transcription of genes involved in TG synthesis, uptake, hydrolysis, and storage (i.e. Fas, Cd36, Lpl, Plin5). Cardiac-specific overexpression of JunD in lean mice led to PPARγ activation, cardiac steatosis, and dysfunction, thereby mimicking the MC phenotype. In DIO hearts as well as in neonatal rat ventricular myocytes exposed to palmitic acid, Ago2 immunoprecipitation, and luciferase assays revealed JunD as a direct target of miR-494-3p. Indeed, miR-494-3p was down-regulated in hearts from obese mice, while its overexpression prevented lipotoxic damage by suppressing JunD/PPARγ signalling. JunD and miR-494-3p were also dysregulated in myocardial specimens from obese patients as compared with non-obese controls, and correlated with myocardial TG content, expression of PPARγ-dependent genes, and echocardiographic indices of LV dysfunction.

Conclusion: miR-494-3p/JunD is a novel molecular axis involved in obesity-related MC. These results pave the way for approaches to prevent or treat LV dysfunction in obese patients.
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http://dx.doi.org/10.1093/eurheartj/ehy903DOI Listing
March 2019

Blood pressure control versus atrial fibrillation management in stroke prevention.

Curr Hypertens Rep 2015 Jun;17(6):553

Clinical and Molecular Medicine Department, Cardiology Unit, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy,

Hypertension is one of the major risk factors for atrial fibrillation which in turn is the most prevalent concomitant condition in hypertensive patients. While both these pathological conditions are independent risk factors for stroke, the association of hypertension and atrial fibrillation increases the incidence of disabling strokes. Moreover, documented or silent atrial fibrillation doubles the rate of cardiovascular death. Lowering blood pressure is strongly recommended, particularly for primary stroke prevention. However, a relatively small percentage of hypertensive patients still achieve the recommended blood pressure goals. The management of atrial fibrillation with respect to stroke prevention is changing. New oral anticoagulants represent a major advancement in long-term anticoagulation therapy in non valvular atrial fibrillation. They have several benefits over warfarin, including improved adherence to the anticoagulation therapy. This is an important issue since non-adherence to stroke prevention medications is a risk factor for first and recurrent strokes.
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http://dx.doi.org/10.1007/s11906-015-0553-1DOI Listing
June 2015

Effects of a long-term treatment with aliskiren or ramipril on structural alterations of subcutaneous small-resistance arteries of diabetic hypertensive patients.

Hypertension 2014 Oct 30;64(4):717-24. Epub 2014 Jun 30.

From the Clinica Medica, Department of Clinical and Experimental Sciences (C.D.C., E.P., M.M., C.R., C.A.R., E.L.B., A.S., B.P., D.R., E.A.R.) and Division of Ophthalmology (S.D., F.S.), University of Brescia, Brescia, Italy; and Division of Cardiology, Department of Clinical and Molecular Medicine (C.S., E.A., A.A., L.S., M.V.) and Surgical Department of Clinical Sciences (P.M.), Biomedical Technologies and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03380DOI Listing
October 2014

The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes.

Clin Sci (Lond) 2013 Aug;125(4):183-9

Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.

In the present study, we tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodelling of resistance arteries in dTGR (double-transgenic rats). dTGR (5 weeks) were treated with aliskiren (3 mg/kg of body mass per day) or ramipril (1 mg/kg of body mass per day) for 14 days and compared with age-matched vehicle-treated dTGR. BP (blood pressure) was similarly reduced in both aliskiren-treated and ramipril-treated rats compared with control dTGR (167±1 and 169±2 mmHg compared with 197±4 mmHg respectively; P<0.05). The M/L (media-to-lumen) ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared with controls (6.3±0.5 and 6.4±0.2% compared with 9.8±0.4% respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME (N(G)-nitro-L-arginine methyl ester) significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren-treated rats. eNOS (endothelial NO synthase) expression showed a 2-fold increase only in aliskiren-treated dTGR as compared with controls (P<0.01) and ramipril-treated dTGR (P<0.05). Plasma nitrite, as an index of NO production, was significantly increased in dTGR treated with either aliskiren or ramipril compared with controls. Only aliskiren induced a 2-fold increase in plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91(phox) expression and ROS (reactive oxygen species) production in aorta were significantly and similarly reduced by both drugs. In conclusion, equieffective hypotensive doses of aliskiren or ramipril reduced the M/L ratio of mesenteric arteries and improved oxidative stress in dTGR. However, only aliskiren increased further NO production in the vasculature. Hence, in dTGR, direct renin inhibition induces favourable effects similar to that induced by ACE (angiotensin-converting enzyme) inhibition in improving vascular remodelling through different mechanisms.
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http://dx.doi.org/10.1042/CS20120395DOI Listing
August 2013

Vascular inflammation and endothelial dysfunction in experimental hypertension.

Int J Hypertens 2011 11;2011:281240. Epub 2011 Sep 11.

Cardiology Unit, Clinical and Molecular Medicine Department, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1037/1039, 00189 Rome, Italy.

Essential hypertension is characterized by increased peripheral vascular resistance to blood flow. The endothelium is a crucial regulator of vascular tone. Its function is impaired in patients with hypertension, with reduced vasodilation, increased vascular tone associated with a proinflammatory and prothrombotic state. Low-grade inflammation localized in vascular tissue is therefore recognized as an important contributor to the pathophysiology of hypertension, to the initiation and progression of atherosclerosis as well as to the development of cardiovascular diseases.
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http://dx.doi.org/10.4061/2011/281240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170891PMC
November 2011