Abstract P215: Angiotensin II-Mediated Cardiac Remodeling in cChAT Mice
It has been demonstrated that the cardiac non-neuronal cholinergic system (NNCS) plays a role in regulating cardiac homeostasis under physiological conditions. To examine a possible role played by NNCS upon cardiac remodeling, we submitted mice with genetic deletion of cardiomyocyte-specific choline acetyltransferase (cChAT) to chronic subcutaneous infusion of angiotensin II (Ang II). Male mice aged six months were assigned into four experimental groups: wild-type (WT) + Saline; WT + Ang II; cChAT + Saline and cChAT + Ang II. Ang II did not change the heart weight in WT mice (10.4±0.3 vs. 8.5±0.2 mg/mm in WT+Saline) but determined an increase in cChAT mice (12.8±1 vs. 8.8±0.6 mg/mm in cChAT+Saline). In WT mice, Ang II decreased left ventricular (LV) fractional shortening (23±2 vs. 35±2 % in WT+Saline) and LV ejection fraction (54±4 vs. 73±2 % in WT+Saline). However, cChAT+Ang II mice exhibited greater decrease in both LV fractional shortening (12±1.8 vs. 23±2 % in WT+Ang II) and ejection fraction (31±4 vs. 54±4 % in WT+Ang II). cChAT mice displayed cardiomyocyte hypertrophy (2002±116 vs. 1377±48 μm2 in WT+Saline) even when receiving saline. Ang II increased the cardiomyocyte surface area in both WT and cChAT mice; however, the cChAT mice exhibited greater myocyte hypertrophy (3035±181 vs. 2603±122 μm2 in WT+Ang II). Hematoxylin and eosin staining revealed that Ang II promoted greater disruption of myocardial structure in cChAT mice. Additionally, Trichrome C staining revealed that WT+Ang II mice presented increased collagen deposition (2.86±0.2 vs. 0.45±0.07 % in WT+Saline); nevertheless, the fibrotic response in cChAT+Ang II mice was greater than that observed in WT animals (6.16±1.1 vs. 2.86±0.2 % in WT+Ang II). Therefore, mice with deficiency for ChAT displayed exacerbated ventricular dysfunction induced by chronic Ang II administration, providing support for a role of the NNCS in the progression of cardiac remodeling.
Author Disclosures: H.C. Salgado: None. G.C.S.V. Tezini: None. A. Roy: None. V.F. Prado: None. R. Gros: None. M.A.M. Prado: None.
- © 2015 by American Heart Association, Inc.