Abstract
Background: The angiotensin-converting enzyme homologue ACE2 and the peptide angiotensin 1-7 (Ang 1-7) have antifibrotic effects, but it is not understood whether they have a protective role in cardiac remodeling. We aimed to analyze the Ang 1-7 Mas receptor and ACE2 expresion levels and their relationship with fibrotic and remodeling factors in human heart failure (HF) and compared them with non-pathological human hearts.Methods: This was a human case-control study in which two groups of samples were analyzed. Controls were organ donors without cardiovascular pathology, but whose heart could not be used for transplantation. Cases were patients with end-stage HF and left ventricle samples were harvested right after the heart transplantation surgery. They were either kept with liquid nitrogen until their analysis or were processed for paraffin embedding. We quantified mRNA expression by real time PCR and ACE2 protein levels by western blot. The collagen deposition was stained by sirius red and quantified with morphometric analysis.Results: Expression of the MMP3 stromelysin mRNA was only detectable in 10 out of 33 pathological samples and in 1 out of 13 control samples. Expression of components of the ACE2 pathway and fibrotic factors were higher in patients with detectable MMP3 expression than in patients with non-detectable MMP3. No differences were found between patients with MMP3 expression or no MMP3 expression regarding etiology, functional class, ventricle dilatation or medication.Conclusions: Only a subset of myocardiums from HF patients is active in the remodeling process at the moment of heart transplantation, as indicated by the MMP3 expression and the higher levels of fibrotic factors. Angiotensin 1-7 Mas receptor expression and ACE2 protein levels are increased in this myocardium subset, suggesting a role for the ACE2 in this process. Overall, we encountered molecular differences in transplanted hearts from patients with similar clinical characteristics.
Highlights
Heart failure (HF) constitutes the end-stage of many cardiopathies and is characterised by a ventricular dysfunction
Samples were classified as either having MMP-3 expression detectable (MMP3) expression detectable (MMP3) in 10 out of 33 patients and in 1 out of 13 controls or as having matrix metalloproteinases (MMP)-3 non-detectable (N-MMP3) in the remaining samples
In this study we have analyzed the left ventricle remodeling stage from a group of end-stage heart failure (HF) patients and found that at a molecular level hearts could be distinguished in two groups; hearts that were currently active in remodeling and hearts that were not
Summary
Heart failure (HF) constitutes the end-stage of many cardiopathies and is characterised by a ventricular dysfunction. The neurohumoral system is activated as a compensatory mechanism when there is a reduction in cardiac output. An increase in circulating levels of hormones such as norepinephrine, angiotensin II (Ang II) and aldosterone triggers a haemodynamic response to preserve cardiac output and blood pressure [3]. Neurohumoral activation is very effective at short-term, over a long period of time, increases the workload of the heart and contributes to further deterioration of ventricular function. The angiotensin-converting enzyme homologue ACE2 and the peptide angiotensin 1-7 (Ang 1-7) have antifibrotic effects, but it is not understood whether they have a protective role in cardiac remodeling. We aimed to analyze the Ang 1-7 Mas receptor and ACE2 expresion levels and their relationship with fibrotic and remodeling factors in human heart failure (HF) and compared them with non-pathological human hearts
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