A concise discussion of the regulatory role of cGMP kinase I in cardiac physiology and pathology

Basic Res Cardiol. 2018 Jun 22;113(4):31. doi: 10.1007/s00395-018-0690-1.

Abstract

The underlying cause of cardiac hypertrophy, fibrosis, and heart failure has been investigated in great detail using different mouse models. These studies indicated that cGMP and cGMP-dependent protein kinase type I (cGKI) may ameliorate these negative phenotypes in the adult heart. Recently, evidence has been published that cardiac mitochondrial BKCa channels are a target for cGKI and that activation of mitoBKCa channels may cause some of the positive effects of conditioning in ischemia/reperfusion injury. It will be pointed out that most studies could not present convincing evidence that it is the cGMP level and the activity cGKI in specific cardiac cells that reduces hypertrophy or heart failure. However, anti-fibrotic compounds stimulating nitric oxide-sensitive guanylyl cyclase may be an upcoming therapy for abnormal cardiac remodeling.

Keywords: ANP; BNP; CNP; Cardiac hypertrophy; Fibrosis; Guanylyl cyclase; Heart failure; NO; PKG; cGMP; cGMP-dependent protein kinase I.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiomegaly / drug therapy
  • Cardiomegaly / enzymology*
  • Cardiomegaly / pathology
  • Cardiomegaly / physiopathology
  • Cardiovascular Agents / therapeutic use
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinase Type I / metabolism*
  • Fibrosis
  • Heart Failure / drug therapy
  • Heart Failure / enzymology*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / enzymology*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardium / enzymology*
  • Myocardium / pathology
  • Second Messenger Systems
  • Ventricular Remodeling* / drug effects

Substances

  • Cardiovascular Agents
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Cyclic GMP-Dependent Protein Kinase Type I
  • Cyclic GMP