Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet

Cardiovascular Diabetology

Marc van Bilsen⁵  Dennis Koehn²  Gustav J. Strijkers¹  Hanneke Cobelens⁴  Chantal Munts⁴  Jos Slenter³  Jurgen W. G. E. van Teeffelen⁴  Mark J. Post⁴  Hans Vink⁴  M. Eline Kooi³  Judith van Haare⁴ 

[1] Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, 1100 DE, The Netherlands;Pie Medical Imaging, Maastricht, 6201 BC, The Netherlands;Department of Radiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6200 MD, The Netherlands;Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6200 MD, The Netherlands;Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6200 MD, The Netherlands

关键词: Glycocalyx;    Cardiac function;    Myocardial perfusion;    Endothelial dysfunction;    Obesity;   

Others  :  1234115
DOI  :  10.1186/s12933-015-0312-2

 received in 2015-07-24, accepted in 2015-11-06,  发布年份 2015

【 摘 要 】

Background

It remains to be established if, and to what extent, the coronary microcirculation becomes compromised during the development of obesity and insulin resistance. Recent studies suggest that changes in endothelial glycocalyx properties contribute to microvascular dysfunction under (pre-)diabetic conditions. Accordingly, early effects of diet-induced obesity on myocardial perfusion and function were studied in rats under baseline and hyperaemic conditions.

Methods

Rats were fed a high fat diet (HFD) for 6 weeks and myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle.

Results

HFD-fed rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. Early diet-induced obesity did not lead to hypertension or cardiac hypertrophic remodeling. In chow-fed, control rats a robust increase in cardiac microvascular perfusion was observed upon adenosine infusion (+40 %; p < 0.05). In contrast, the adenosine response was abrogated in rats on a HFD (+8 %; N.S.). HFD neither resulted in rarefaction or loss of glycocalyx integrity in skeletal muscle, nor reduced staining intensity of the glycocalyx of cardiac capillaries.

Conclusions

Alterations in coronary microcirculatory function as assessed by first-pass perfusion MRI represent one of the earliest obesity-related cardiac adaptations that can be assessed non-invasively. In this early stage of insulin resistance, disturbances in glycocalyx barrier properties appeared not to contribute to the observed changes in coronary microvascular function.

【 授权许可】

   
2015 van Haare et al.

【 图 表 】

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