In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects... Show moreIn neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover. Myocardial collagen turnover can be assessed by plasma PINP, PIIINP, and ICTP representing collagen synthesis (PINP, PIIINP) or degradation (ICTP). We investigated the effects of cardiac resynchronization therapy (CRT) on collagen turnover in patients at baseline and after 6 months of CRT (chapter 3). Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and RV failure are associated with MMP activation in RV, we investigated whether NO plays role in RV hypertrophy and failure (chapter 4). In chapter 5 we reviewed novel approaches to treat experimental PAH. We investigated whether MCT-induced PAH and RV failure can be treated with mesenchymal stem cells (MSCs) from donor rats with PAH caused by MCT. At day 14 after MCT, recipient rats were treated with MSCs. In chapters 6,7 the effects of MSCs on pulmonary pathology and RV function were examined. Isolated cardiomyocytes were investigated for PAH-related changes in excitability. In chapter 8 we reported on excitability properties dependent on Kv-channel expression, proposed to play a role in arrhythmias. Show less
Identification of translational and/or post-translational modifications of cardiac proteins after acute myocardial infarction (AMI) or during the progression to congestive heart failure (CHF) is... Show moreIdentification of translational and/or post-translational modifications of cardiac proteins after acute myocardial infarction (AMI) or during the progression to congestive heart failure (CHF) is relevant to gain insight into the pathological mechanisms. Characterization of the release kinetics of these cardiac proteins from the reversibly or irreversibly injured myocardium into the circulation may lead to new diagnostic biomarkers. Although cardiac Troponin I (cTnI) is a well-known biomarker of irreversible myocardial damage in acute myocardial infarction, we demonstrated that the release of cTnI also occurs from viable cardiomyocytes by a stretch-related mechanism, mediated by integrin stimulation. This finding may explain why in several pathological conditions, such as CHF, plasma cTnI levels are elevated in the absence of myocardial necrosis. In addition, we investigated the role of Tenascin-C re-expression during the development of heart failure and the relevance of TNC as a biomarker of ventricular remodeling. In animals with pressure-overload induced ventricle dilatation, TNC gene expression was upregulated, resulting in re-expression of myocardial TNC protein levels and elevated TNC plasma levels, correlating with cardiac function. Plasma TNC levels in patients with CHF declined during cardiac resynchronization therapy. This study indicates that serial plasma TNC levels can be used as a marker of adverse or reverse ventricular remodeling. Show less
