B. Svezia

Myocardial Expression Analysis of Osteopontin and Its Splice Variants in Patients Affected by End-Stage Idiopathic or Ischemic Dilated Cardiomyopathy

Osteopontin (OPN) is a phosphoglycoprotein of cardiac extracellular matrix and it is still poorly defined whether its expression changes in failing heart of different origin. The full-length OPN-a and its isoforms (OPN-b, OPN-c) transcriptomic profile were evaluated in myocardium of patients with dilated or ischemic cardiomyopathy (DCM n = 8; LVEF% = 17.5±3; ICM n = 8; LVEF% = 19.5±5.2) and in auricle of valvular patients (VLP n = 5; LVEF%≥50), by Real-time PCR analysis. OPN-a and thrombin mRNA levels resulted significantly higher in DCM compared to ICM patients (DCM:31.3±7.4, ICM:2.7±1.1, p = 0.0002; DCM:19.1±4.9, ICM:5.4±2.2, p = 0.007, respectively). Although both genes’ mRNA levels increased in patients with LVEF<50% (DCM+ICM) with respect to VLP with LVEF>50%, a significant increase in OPN (p = 0.0004) and thrombin (p = 0.001) expression was observed only in DCM. In addition, a correlation between OPN-a and thrombin was found in patients with LVEF<50% (r = 0.6; p = 0.003). The mRNA pattern was confirmed by OPN-a cardiac protein concentration (VLP:1.127±0.26; DCM:1.29±0.22; ICM:1.00±0.077 ng/ml). The OPN splice variants expression were detectable only in ICM (OPN-b: 0.357±0.273; OPN-c: 0.091±0.033) and not in DCM patients. A significant correlation was observed between collagen type I, evaluated by immunohistochemistry analysis, and both OPN-a mRNA expression (r = 0.87, p = 0.002) and OPN protein concentrations (r = 0.77, p = 0.016). Concluding, OPN-a and thrombin mRNA resulted dependent on the origin of heart failure while OPN-b and OPN-c highlighted a different expression for DCM and ICM patients, suggesting their correlation with different clinical-pathophysiological setting.

The apelin/APJ mRNA profile in left ventricular tissue of patients with idiopathic or ischemic end-stage dilated cardiomyopathy

Published on behalf of the European Society of Cardiology. All rights reserved.

Dipyridamole-induced C-type natriuretic peptide mRNA overexpression in a minipig model of pacing-induced left ventricular dysfunction

Dipyridamole (DP) restores ischemic tissue blood flow stimulating angiogenesis in eNOS-dependent pathways. C-type natriuretic peptide (CNP) is expected to mimic the migration-stimulatory effect of NO via a cGMP-dependent mechanism. Aim of this study was to assess the role of concomitant treatment with DP on CNP levels in blood and myocardial tissue of minipigs with left ventricular dysfunction (LVD) induced by pacing at 200bpm in the right ventricular apex. Minipigs with DP therapy (DP+, n=4) or placebo (DP-, n=4) and controls (C-SHAM, n=4) underwent 2D-EchoDoppler examination and blood collection before and after 4 weeks of pacing, when cardiac tissue was collected. Histological/immunohistochemical analyses were performed. CNP levels were determined by radioimmunoassay; cardiac CNP, BNP, natriuretic receptors expression by Real-Time PCR. After pacing, cardiac parameters resulted less impaired in DP+ compared to DP-. Histological sections presented normal morphology while the arteriolar density resulted: C-SHAM: 9.0±1.2; DP-: 4.9±0.3; DP+: 6.5±0.6number/mm(2); C-SHAM vs DP- and DP+ p=0.004, p=0.04, respectively. CNP mRNA resulted lower in DP- compared to C-SHAM and DP+ as well as NPR-B (p=0.011, DP- vs DP+). Both NPR-A/NPR-C mRNA expressions were significantly (p<0.001) lower both in DP- and DP+ compared to C-SHAM. BNP mRNA was higher in LVD. CNP plasma levels showed a similar trend with respect to gene expression (C-SHAM: 30.5±15; DP-: 18.6±5.5; DP+: 21.2±4.7pg/ml). These data suggest that DP may serve as a preconditioning agent to increase the protective CNP-mediated endocrine response in LVD. This response, mediated by its specific receptor NPR-B, may offer new insights into molecular targets for treatment of LVD.

New cardiac expression of two adenosine-2A receptor isoforms in dysfunctioning minipigs

Abstract Purpose: Eight A2AR variants are reported in humans while no A2AR isoforms in pigs. The aim of this study was to evaluate potential isoforms presence in cardiac pig tissue to better define possible involvement of A2AR in the cardiovascular pathophysiology. Materials and methods: In adult male minipigs (n = 4) left ventricular dysfunction (LVD) was induced by pacing at 200 bpm in the right ventricular (RV) apex. In these animals and in sham operated pigs (C-SHAM, n = 4) cardiac tissue was collected from LV-septal wall (LV-SW)-close to pacing site-and from lateral (opposite) site (LV-OSW). A2AR specific primers, derived from Sus scrofa AY772412 sequence, were used for Real-Time PCR. The DNA was sequenced using the Sanger method. Histological analysis was also performed. Results: In LV-SW of LVD minipigs the A2AR melting curves were characterized by a sharp peak between 87 and 91 °C (short isoform, 1–94 bp) on the right of the principal peak corresponding to a long A2AR isoform (GenBank: JQ229674.1) 1–213 bp. As for C-SHAM only one peak was observed in LV-OSW region of LVD animals. The short isoform had an alternative promoter region and a specific translated protein. Histology showed in LVD-LV-SW prominent Purkinje cells compared to LV-OSW and C-SHAM. No difference in A2AR expression was observed between LVD animals and C-SHAM although a slight decrease was observed in LVD-LV-OSW. Conclusions: The presence of two different isoforms in the myocardium close to the insertion of pacing is suggestive of a differential state-specific expression of A2AR in cardiac tissue.

Grapevine microRNAs in an in vitro model of cell line: new potential insight on their role in the setting of human health.

Recent trends in diagnostic work-up among unselected patients newly diagnosed with heart failure : a Swedish population-based studyMitral regurgitation severity correlates with symptoms and extent of left atrial dysfunction : effect of mitral valve repairHeart failure can occur in any age, no depend on sex, but in men and women the mechanism, even if is the same, the fact is that the compromise on pumping function is diferent. AIM We realized a follow-up with 100 female patients during hospitalization with heart failure as a mean diagnostic. These are patient between 60 and 75 years old, with different pathologies: diabetes mellitus, arterial hypertension, obesity, atrial fibrillation, and hypothyroidism. We observed their treatment comparing with a control group (100 men in heart failure) by administering vasodilator and diuretic drugs. Performed echocadiography doppler control, daily renal function, NT pro BNP levels control, oxide nitric response. Results: We observed that ventricular dilation, hypertrophy as tachycardia is more typical in men. Our group demonstrated very fast response to beta blockers and diuretics. The ejection fraction increased in 10-15% faster than in control group. Oxide nitric had not the result we expected. But in men the effect is very high. NT pro BNP levels no were increased as a control group. Recovering renal function in women during heart failure depends on risk factors as diabetes mellitus, obesity, more characteristics for women. Conclusions: In women heart failure has the same mechanism that in men, but more of the cardiac compensatory mechanisms during heart failure as Frank-Starling mechanism, ventricular dilation or hypertrophy and tachycardia present more complications in men; women recover sinus rhythm faster than men, hypertrophy is not characteristic and dilation recovers EF as pumping function is near normal. We do not observed increased sympathetic adrenergic activity in our patients and increased vagal activity to heart. Renin-angiotensin-aldosterone and antidiuretic hormone systems in women is compensated by vasoconstriction improving ventricular stroke volume by reducing afterload on the ventricle. Table 3. NT-pro BN characteristics NT-proBNP cutoff value of 125 pg/mL had the best sensitivity-to-specificity ratio and NPV to rule out asymptomatic LV moderate to severe diastolic or systolic dysfunction in patients at risk for heart failure: 1. Men younger than 60 years (sensitivity, 87.5%; specificity, 92.7%; NPV, 99.5%; positive predictive value [PPV], 33.3%) 2. Women younger than 60 years (sensitivity, 100%; specificity, 84.1%; NPV, 100%; PPV, 33.3%) 3. Men at least age 60 years (sensitivity, 100%; specificity, 77.1%; NPV, 100%; PPV, 32.5%) 4. Women at least age 60 years (sensitivity, 100%; specificity, 69.9%; NPV, 100%; PPV, 21%)

Myocardial expression analysis of osteopontin splice variants in patients affected by end-stage dilated or ischemic cardiomyopathy

Successful reperfusion is associated with lower levels of markers of myocardial damage and dysfunction in ST-elevation but not in non-ST-elevation myocardial infarction : insights from the PLATO trialBackground: Carbohydrate antigen 125 (CA125) is a mucin produced by serosal cells in response to mechanical and inflammatory stimuli. CA125 has emerged as prognostic biomarker in heart failure (HF) and correlates with markers of fluid overload, echocardiographic parameters and prognosis in HF patients. In patients with acute coronary syndrome (ACS), elevated CA125 is correlated with a higher risk of in-hospital HF. The relationship between CA125 and long-term prognosis in ACS patients has not previously been assessed. Purpose: The purpose of our study was to investigate if CA125 measured at the time of an acute coronary event is related to cardiac remodeling during the first year of follow-up and long-term risk for HF and death Methods: We measured CA125 in plasma within 24 hours of the acute event in 523 patients with acute myocardial infarction or unstable angina admitted to the Coronary Care Unit. Routine echocardiograms were performed in all participants. The primary outcomes were hospitalization with a diagnosis of heart failure or death during follow-up, identified through data from the Swedish Hospital Discharge Register and the Swedish Cause of Death Register. In a subgroup of 109 patients aged 75 years or above we assessed the relationships between baseline CA125 and echocardiographical parameters of cardiac structure and function at 1 year after the index ACS. Results: The median follow-up period was 27.3 months for incident HF and 39.5 months for mortality. In Cox proportional hazards models we found an adjusted hazard ratio of 1.51 (95% CI 1.08-2.12; p (Less)

Corrigendum to “Adrenomedullin and intermedin gene transcription is increased in leukocytes of patients with chronic heart failure at different stages of the disease” [Peptides 55 (2014) 13–16]

of original article: http://dx.doi.org/10.1016/j.peptides.2014.01.028.Corresponding author at: CNR Institute of Clinical Physiology, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy. Tel.: +39 050 3152793; fax: +39 050 3152166.E-mail address: delry@ifc.cnr.it (S. Del Ry).http://dx.doi.org/10.1016/j.peptides.2014.05.0010196-9781/© 2014 Elsevier Inc. All rights reserved.