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Cardiac acetylcholine inhibits ventricular remodeling and dysfunction under pathologic conditions
FASEB Journal
  • Ashbeel Roy, Robarts Research Institute
  • Mouhamed Dakroub, Robarts Research Institute
  • Geisa C.S.V. Tezini, Western University
  • Yin Liu, Robarts Research Institute
  • Silvia Guatimosim, Universidade Federal de Minas Gerais
  • Qingping Feng, Western University
  • Helio C. Salgado, Universidade de São Paulo
  • Vania F. Prado, Robarts Research Institute
  • Marco A.M. Prado, Robarts Research Institute
  • Robert Gros, Robarts Research Institute
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Autonomic dysfunction is a characteristic of cardiac disease and decreased vagal activity is observed in heart failure. Rodent cardiomyocytes produce de novo ACh, which is critical in maintaining cardiac homeostasis. We report that this nonneuronal cholinergic system is also found in human cardiomyocytes, which expressed choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT). Furthermore, VAChT expression was increased 3- and 1.5-fold at the mRNA and protein level, respectively, in ventricular tissue from patients with heart failure, suggesting increased ACh secretion in disease. Weusedmicewith geneticdeletionof cardiomyocytespecificVAChTor ChATandmice overexpressingVAChT to test the functional significance of cholinergic signaling. Mice deficient for VAChT displayed an 8% decrease in fractional shortening and 13% decrease in ejection fraction comparedwith angiotensin II (Ang II)-treated control animals, suggesting enhanced ventricular dysfunction and pathologic remodeling in response to Ang II. Similar results were observed in ChAT-deficient mice. Conversely, no decline in ventricular function was observed in Ang II-treated VAChT overexpressors. Furthermore, the fibrotic area was significantly greater (P < 0.05) in Ang II- treated VAChT-deficient mice (3.61 ± 0.64%) compared with wild-type animals (2.24±0.11%). In contrast, VAChT overexpressing mice didnot display an increase in collagen deposition. Our results provide new insight into cholinergic regulation of cardiac function, suggesting that a compensatory increase in cardiomyocyte VAChT levels may help offset cardiac remodeling in heart failure.

Citation Information
Ashbeel Roy, Mouhamed Dakroub, Geisa C.S.V. Tezini, Yin Liu, et al.. "Cardiac acetylcholine inhibits ventricular remodeling and dysfunction under pathologic conditions" FASEB Journal Vol. 30 Iss. 2 (2016) p. 688 - 701
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