Aoqui Cristiane, Chmielewski Stefan, Scherer Elias, Eissler Ruth, Sollinger Daniel, Heid Irina, Braren Rickmer, Schmaderer Christoph, Megens Remco Ta, Weber Christian, Heemann Uwe, Tschöp Matthias, Baumann Marcus
Department of Nephrology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger St, 22, Munich 81675, Germany.
Cardiovasc Diabetol. 2014 Feb 3;13:31. doi: 10.1186/1475-2840-13-31.
Metabolic 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.
Development 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.
I-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.
We 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.
代谢综合征（MetS）与心血管疾病（CVD）风险增加相关。多种类型CVD病理生理学的一个重要特征是微血管功能障碍。尽管MetS的各个组成部分本身就是CVD的危险因素，但当将该综合征视为一个整体时，风险会增加。我们旨在描述MetS发展过程中的微血管功能及其一些影响因素。
研究了高脂饮食（HFD，51%的能量来自脂肪）喂养的C57BL/6小鼠中MetS的发展情况。MetS的初始阶段（I-MetS）定义为HFD喂养的前2周，完全发展阶段在HFD喂养8周后出现。我们通过评估肥胖、血压和微血管功能的变化来描述这些阶段。所有数据均以平均值±标准误差（SEM）表示。使用非线性回归分析计算肌动描记实验累积剂量-反应曲线之间的差异。在其他实验中，两组之间的比较采用学生t检验。多组之间的比较采用单因素方差分析和Tukey事后检验。概率值<0.05被认为具有统计学意义。
I-MetS小鼠出现体重增加、血压升高以及以血管收缩增强为特征的微血管功能障碍。这一发现与完全发展的MetS小鼠的情况相反，与内皮功能障碍、胰岛素抵抗或全身炎症无关。在初始阶段，血管周围脂肪组织没有炎症迹象，对血管收缩模式也没有影响。这些发现表明，MetS中高血压的发生受到血管平滑肌细胞功能障碍的强烈影响，并且独立于已知影响微血管功能进而影响血压水平的重要因素。
我们在I-MetS中发现了孤立的血管收缩增强以及血压升高的情况，但没有发现已知影响微血管功能的经典MetS组成部分。这些发现增进了我们对与MetS相关的CVD风险病理生理学的理解。
