JACC: Basic to Translational Science (Dec 2016)

Cardiac-Directed Expression of Adenylyl Cyclase Catalytic Domain Reverses Cardiac Dysfunction Caused by Sustained Beta-Adrenergic Receptor Stimulation

  • Mei Hua Gao, PhD,
  • N. Chin Lai, PhD,
  • Dimosthenis Giamouridis, MSc,
  • Young Chul Kim, PhD,
  • Zhen Tan, PhD,
  • Tracy Guo, BS,
  • Wolfgang H. Dillmann, MD,
  • Jorge Suarez, PhD,
  • H. Kirk Hammond, MD

DOI
https://doi.org/10.1016/j.jacbts.2016.08.004
Journal volume & issue
Vol. 1, no. 7
pp. 617 – 629

Abstract

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Transgenic mice with cardiac-directed C1C2, a fusion protein of the intracellular C1 and C2 segments of adenylyl cyclase type 6, had normal left ventricular (LV) function, but diminished cAMP generation. Cardiac myocytes from C1C2 mice showed increased Ca2+ release. Mice underwent continuous isoproterenol infusion to stress the heart. In C1C2 mice, sustained isoproterenol infusion increased rather than decreased LV function. LV SERCA2a and Ca2+ release were increased. Reduced cAMP generation and resistance to catecholamine cardiomyopathy are attractive features of this potential heart failure therapeutic.

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