PhD Scientific Days 2017

Oral Presentations: Cardiovascular

Targeting the nitric oxide-unresponsive soluble guanylate cyclase in a rat model of pressure overload induced left ventricular myocardial hypertrophy and heart failure

Előadó neve

Dr. Ruppert, Mihály

Előadó munkahelye

Heart and Vascular Center, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

+36305045060

Előadó e-mail címe

ruppertmis@gmail.com

Az előadás címe

Targeting the nitric oxide-unresponsive soluble guanylate cyclase in a rat model of pressure overload induced left ventricular myocardial hypertrophy and heart failure

Szerző(k) neve és munkahelye

Mihály Ruppert1,2, Tamás Radovits2, Sevil Korkmaz-Icöz1, Shiliang Li1, Péter Hegedűs1, Balázs Tamás Németh2, Oláh Attila2, Csaba Mátyás2, Kálmán Benke2, Béla Merkely2, Matthias Karck1, Gábor Szabó1
1 Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany;
2 Heart and Vascular Center, Semmelweis University, Budapest, Hungary

Szekció

Oral Presentations: Cardiovascular

Data of the presenter

Doctoral School: Basic Medicine
Program: Cardiovascular Disorders, Physiology and Medicine of Ischaemic Circulatory Diseases
Supervisor: Tamás Radovits
E-mail address: ruppertmis@gmail.com

Text of the abstract

Introduction: Chronic pressure overload of the left ventricle induces the manifestation of pathological left ventricular myocardial hypertrophy (LVH) that entails gradual deterioration of cardiac function. Recently, preclinical studies have indicated that the impairment of the soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) – protein kinase G signaling contributes to the development of LVH associated cardiac dysfunction.
Aims: Therefore we investigated the effect of the sGC activator cinaciguat in a rat model of pressure overload-induced LVH and heart failure.
Methods: Abdominal aortic banding (AB) was carried out to induce pressure overload for 6 or 12 weeks. Sham operated animals served as controls. The experimental groups were treated from the 7th to the 12th postoperative week, with 10 mg/kg/day cinaciguat (Cin) or with placebo (Co) p.o., respectively. The temporal development of LVH and its progression to heart failure was investigated by serial echocardiography. Cardiac function was assessed by pressure-volume analysis. In addition, histological and molecular biological measurements were also performed.
Results: In the cinaciguat treated aortic banded group decreased heart weight-to-tibial length ratio (HW/TL ratio: 0.57±0.02 vs. 0.48±0.02g/cm, p<0.05 AB 12th week-Co week vs. AB 12th week-Cin) decreased cardiomyocyte diameter (CD: 23.94±0.59 vs. 20.02±0.20μm, p<0.05 AB 12th week-Co week vs. AB 12th week-Cin) and reduced myocardial expression levels of atrial natriuretic peptide and β/α-myosin heavy chain ratio were detected. Furthermore, we observed, that chronic activation of the sGC by cinaciguat provided protection against the increased interstitial fibrosis (Masson’s score: 1.7±0.2 vs. 1.2±0.1, P<0.05 AB 12week-Co vs. AB 12week-Cin) and nitro-oxidative stress. The prevention of the pathological structural alterations was accompined by improved cardiac function (ejection fraction: 47.4±2.7 vs. 63.7±2.4%, P<0.05 AB 12week-Co vs. AB 12week-Cin).
Conclusion: Our results demonstrate that chronic activation of the sGC enzyme prevents the transition from pressure overload-induced LVH to heart failure.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1039

Authors (legacy)

Mihály Ruppert1,2, Tamás Radovits2, Sevil Korkmaz-Icöz1, Shiliang Li1, Péter Hegedűs1, Balázs Tamás Németh2, Oláh Attila2, Csaba Mátyás2, Kálmán Benke2, Béla Merkely2, Matthias Karck1, Gábor Szabó1
1 Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany;
2 Heart and Vascular Center, Semmelweis University, Budapest, Hungary