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Progressive Decrease in Coronary Vascular Function Associated With Type 2 Diabetic Heart Disease.

Rajesh Katare1, James T Pearson2,3, Jason Kar-Sheng Lew1

  • 1Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.

Frontiers in Physiology
|June 22, 2018
PubMed
Summary
This summary is machine-generated.

Diabetic heart disease involves independent cardiac and coronary dysfunction, not solely linked to blood flow issues. The Rho-kinase pathway may be a key factor in diabetic heart disease progression.

Keywords:
angiographycardiac dysfunctioncoronary blood flowdb/db mouseendothelial dysfunction

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Area of Science:

  • Cardiovascular Research
  • Diabetology
  • Vascular Biology

Background:

  • Diabetic heart disease (DHD) pathogenesis is not fully understood.
  • Myocardial function relies on adequate coronary blood flow.
  • Endothelial dysfunction in diabetes suggests early vascular involvement.

Purpose of the Study:

  • To investigate if impaired coronary perfusion contributes to DHD or if cardiac and coronary dysfunction are independent diabetic pathologies.
  • To determine the role of the Rho-kinase pathway in DHD.

Main Methods:

  • Synchrotron radiation microangiography to assess coronary circulation in type-2 diabetic (db/db) and non-diabetic (db/+) mice.
  • Vascular function assessment via vasodilatory responses to acetylcholine, sodium nitroprusside, and fasudil.
  • Echocardiography for cardiac function and immunohistochemistry for eNOS and ROCK expression.

Main Results:

  • Diabetic mice showed normal cardiac and coronary function at 8 weeks, but cardiac dysfunction by 16 weeks.
  • Coronary perfusion remained normal until 24 weeks, when significant coronary vascular dysfunction was observed.
  • Fasudil treatment restored coronary perfusion in diabetic mice by dilating constricted vessels, correlating with decreased eNOS and increased ROCK expression.

Conclusions:

  • Cardiac and coronary dysfunction in DHD appear to originate independently in diabetes.
  • The Rho-kinase pathway is implicated in the onset and progression of diabetic heart disease.