Abstract 2096: LVAD Therapy Up-Regulates ACE-2 but May Decrease Apoptosis & Mediate Reverse Remodeling via a “Non Ang 1–7 - Non mas Receptor” Pathway In Patients With End Stage Heart Failure.
Background: The ACE-2 gene product counteracts the traditional ACE/Angiotensin II pathway & protects against Heart Failure (HF). However, the behavior of ACE-2, its product Ang 1–7 & its newly discovered mas receptor, before & after Left Ventricular Assist Devices (LVAD), has not been studied.
Hypothesis: LVAD will augment ACE-2 pathway & this, via its anti-apoptotic effect through an increase in Ang 1–7 & mas, might help reverse remodeling.
Methods: We measured myocardial ACE-2, Ang 1–7 & mas receptor mRNA (Real Time PCR) & proteins (western blots, ELISA & immunohistochemistry), in non-scar myocardium from patients with HF at LVAD implantation & transplant (n=6, ischemic in 4, LVAD to transplant: 151– 681 days) & 3 controls. Myocyte apoptosis (apologix stain) & ventricular remodeling (Echo) were measured. Anti apoptotic effect of Ang 1–7 & mas receptor activation (with/without a mas blocker - ala-D) was also tested in myocyte culture.
Results: ACE-2 (mRNA + protein) decreased in HF but was significantly up-regulated by LVAD & this correlated with less myocyte apoptosis & reverse remodeling. Surprisingly, while both Ang 1–7 & mas receptor activation specifically reduced apoptosis in cardiomyocyte culture, their levels were not significantly changed post LVAD & did not correlate with in-vivo apoptosis or remodeling.
Conclusions: We show for the first time that ACE-2 is reduced in human end-stage heart failure and this is significantly reversed with LVAD therapy. In contrast, Ang 1–7 & its mas receptor, the logical pathways for ACE-2 action are not increased. ACE-2 up-regulation, while beneficial post LVAD, seems to mediate these benefits via a “non Ang 1–7 - non mas receptor pathway”.