Microvascular dysfunction in the course of metabolic syndrome induced by high-fat diet

Cardiovascular Diabetology

Original Investigation

Ruth Eißler¹  Uwe Heemann¹  Cristiane Aoqui¹  Marcus Baumann¹  Daniel Sollinger¹  Christoph Schmaderer¹  Stefan Chmielewski²  Elias Scherer³  Remco TA Megens⁴  Christian Weber⁵  Matthias Tschöp⁶  Rickmer Braren⁷  Irina Heid⁷ 

[1] Department of Nephrology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger St. 22, 81675, Munich, Germany;Department of Nephrology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger St. 22, 81675, Munich, Germany;Department of Human Molecular Genetics, Laboratory of High-throughput Technologies, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland;Dept of Otorhinolaryngology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany;Institute for Cardiovascular Prevention, Ludwig-Maximilian-Universität, Munich, Germany;Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands;Institute for Cardiovascular Prevention, Ludwig-Maximilian-Universität, Munich, Germany;Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands;German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany;Institute for Diabetes and Obesity, Helmholtz Zentrum München, Munich, Germany;Institute of Radiology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany;

关键词: High-fat diet;    Metabolic syndrome;    Hypertension;    Microvascular dysfunction;    Vasoconstriction;   

DOI  :  10.1186/1475-2840-13-31

 received in 2014-01-28, accepted in 2014-01-29,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMetabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). One important feature underlying the pathophysiology of many types of CVD is microvascular dysfunction. Although components of MetS are themselves CVD risk factors, the risk is increased when the syndrome is considered as one entity. We aimed to characterize microvascular function and some of its influencing factors in the course of MetS development.MethodsDevelopment of MetS in C57BL/6 mice on a high-fat diet (HFD, 51% of energy from fat) was studied. The initial phase of MetS (I-MetS) was defined as the first 2 weeks of HFD feeding, with the fully developed phase occurring after 8 weeks of HFD. We characterized these phases by assessing changes in adiposity, blood pressure, and microvascular function. All data are presented as mean ± standard error (SEM). Differences between cumulative dose–response curves of myograph experiments were calculated using non-linear regression analysis. In other experiments, comparisons between two groups were made with Student’s t-test. Comparisons between more than two groups were made using one-way ANOVA with Tukey post-hoc test. A probability value <0.05 was considered statistically significant.ResultsI-MetS mice presented with weight gain, blood pressure elevation, and microvascular dysfunction characterized by augmented vasoconstriction. This finding, contrary to those in mice with fully developed MetS, was not associated with endothelial dysfunction, insulin resistance, or systemic inflammation. In the initial phase, perivascular adipose tissue showed no sign of inflammation and had no influence on the pattern of vasoconstriction. These findings suggest that the onset of hypertension in MetS is strongly influenced by vascular smooth muscle cell dysfunction and independent of important factors known to influence microvascular function and consequently blood pressure levels.ConclusionWe identified in I-MetS the occurrence of isolated augmented vasoconstriction along with blood pressure elevation, but not the presence of classical MetS components known to influence microvascular function. These findings increase our understanding of the pathophysiology of CVD risk associated with MetS.

【 授权许可】

Unknown   
© Aoqui et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.