Clinical & Experimental Cardiology
Open Access

Abstract

Molecular Changes of the Angiotensin Converting Enzyme 2 Pathway in Myocardial Tissue from Heart Failure Patients Undergoing Heart Transplantation

Montserrat Batlle, Eulàlia Roig, Maria Josep Pulgarin, Begoña Campos, José Ramírez, Jose Luis Pomar, Marta Farrero, Maria Ángeles Castel, Montserrat Cardona, Mercé Roqué, Josefina Orús, Ramon Cartaña and Fèlix Perez-Villa

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.