Myocardial α2-Adrenoceptors as Therapeutic Targets to Prevent Cardiac Hypertrophy and Heart Failure

被引：3
作者：
Pimenov O.Y. [1 ]
Galimova M.H. [1 ]
Evdokimovskii E.V. [1 ]
Averin A.S. [1 ]
Nakipova O.V. [2 ]
Reyes S. [3 ]
Alekseev A.E. [1 ,3 ]
机构：
[1] Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290, Moscow oblast
[2] Institute Cell Biophysics, Russian Academy of Sciences, Pushchino, 142290, Moscow oblast
[3] Department of Cardiovascular Medicine, Center for Regenerative Medicine, Stabile 5, Mayo Clinic, Rochester, MN
来源：
Biophysics | 2019年 / 64卷 / 5期
基金：
俄罗斯科学基金会;
关键词：
angiotensin; Ca[!sup]2+[!/sup] homeostasis; G-proteins; gene therapy; intracellular signaling; Keywords: cell-based therapy;
D O I：
10.1134/S000635091905021X
中图分类号：
学科分类号：
摘要：
Abstract—Aberrations in mechanisms of cardiac adaptation to catecholamine overflow can result in maladaptive cardiac hypertrophy and heart failure. Currently available heart failure therapies fall short of expectations, warranting their refinement via a paradigm shift from treatment of secondary factors of heart failure (neurohormonal activation, renal dysfunction, etc.) to direct heart targeting with the goal of improving the cardiac structure and function. We have detected expression of α2-adrenergic receptor (α2-AR) isoforms not only in adult cardiomyocytes, but also in the embryonic heart throughout its development from embryonic stem cells. In addition to known suppression of the sympathoadrenal system activity, α2-ARs play protective and adaptive roles in cardiomyocytes. This review analyzes cardiomyocyte α2-AR signaling, which counteracts intracellular Ca2+ overload and angiotensin-induced cardiac hypertrophy. We suppose that in heart failure-linked desensitization of these receptors, cardiac-specific cell- or gene-based therapies aimed at repairing or amplifying α2-AR signaling could offer prospects for a prevention of cardiac hypertrophy and heart failure. © 2019, Pleiades Publishing, Inc.
引用
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页码：738 / 750
页数：12
相关论文
共 163 条
  • [1] Mareev V.Y., Ageev F.T., Arutyunov G.P., Serdechnaya Nedostatochnost, 7, (2013)
  • [2] McMurray J.J., Pfeffer M.A., Lancet, 365, (2005)
  • [3] Neubauer S., N. Engl. J. Med., 356, (2007)
  • [4] Eisenhofer G., Friberg P., Rundqvist B., Circulation, 93, (1996)
  • [5] Dzimiri N., Pharmacol. Rev., 51, (1999)
  • [6] Ashrafian H., Redwood C., Blair E., Trends Genet., 19, (2003)
  • [7] Kehat I., Molkentin J.D., Circulation, 122, (2010)
  • [8] Drazner M.H., Circulation, 123, (2011)
  • [9] Ahlquist R.P., J. Auton. Pharmacol., 1, (1980)
  • [10] Bylund D.B., Am. J. Physiol., 293, (2007)
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