Barac Ana, Campia Umberto, Matuskey Linda A, Lu Li, Panza Julio A
Cardiovascular Research Institute at the Washington Hospital Center, Washington, DC, USA.
Am J Cardiol. 2008 Apr 1;101(7):980-5. doi: 10.1016/j.amjcard.2007.11.058.
Adipokines are substances produced by the adipose tissue that may play significant roles in the mechanisms contributing to the development of atherosclerosis. Thiazolidinediones have been shown to improve endothelium-dependent vasodilation and to exert multiple antiatherosclerotic effects. This study tested the hypotheses that nondiabetic patients with cardiovascular risk factors have altered levels of adipokines that can be modified by pioglitazone treatment. Eighty patients with hypertension or hypercholesterolemia were in a double-blinded, placebo-controlled, crossover study. In each treatment phase, patients received pioglitazone 45 mg/day or placebo for 8 weeks. Endothelial function studies and biochemical assays were performed at the end of each 8-week treatment period. Twenty-two normal volunteers, matched with patients for age, gender, and body mass index, were recruited as a control group. Compared with controls, placebo-treated patients had lower adiponectin levels (11,160 +/- 763 vs 6,078 +/- 385 ng/ml, p <0.001) and similar plasma leptin levels (21.5 +/- 3.8 vs 16.2 +/- 1.5 ng/ml, p = 0.128) and resistin levels (5.1 +/- 0.4 vs 4.4 +/- 0.2 ng/ml, p = 0.250). In patients, pioglitazone treatment markedly increased adiponectin (+121%, p <0.001) and decreased resistin (-10.5%, p = 0.03). Leptin was not significantly decreased (-7.1%, p = 0.10). In multivariate analysis, pioglitazone-induced changes in endothelial reactivity to acetylcholine were the only significant predictor of increases in adiponectin. In conclusion, in nondiabetic patients with major cardiovascular risk factors, pioglitazone treatment beneficially influences circulating adipokine levels. The relation between the increase in adiponectin levels and the improvement in endothelial vasodilator activity suggests a mechanistic link between vascular effects and adiponectinemia.
脂肪因子是由脂肪组织产生的物质，可能在动脉粥样硬化发展机制中发挥重要作用。噻唑烷二酮类药物已被证明可改善内皮依赖性血管舒张，并发挥多种抗动脉粥样硬化作用。本研究检验了以下假设：患有心血管危险因素的非糖尿病患者体内脂肪因子水平发生改变，且吡格列酮治疗可对其进行调节。80例高血压或高胆固醇血症患者参与了一项双盲、安慰剂对照、交叉研究。在每个治疗阶段，患者接受45毫克/天的吡格列酮或安慰剂治疗8周。在每个8周治疗期结束时进行内皮功能研究和生化检测。招募了22名年龄、性别和体重指数与患者匹配的正常志愿者作为对照组。与对照组相比，接受安慰剂治疗的患者脂联素水平较低（11,160±763对6,078±385纳克/毫升，p<0.001），血浆瘦素水平相似（21.5±3.8对16.2±1.5纳克/毫升，p = 0.128），抵抗素水平相似（5.1±0.4对4.4±0.2纳克/毫升，p = 0.250）。在患者中，吡格列酮治疗显著增加了脂联素（+121%，p<0.001）并降低了抵抗素（-10.5%，p = 0.03）。瘦素没有显著降低（-7.1%，p = 0.10）。在多变量分析中，吡格列酮诱导的内皮对乙酰胆碱反应性变化是脂联素增加的唯一显著预测因素。总之，在患有主要心血管危险因素的非糖尿病患者中，吡格列酮治疗有益地影响循环脂肪因子水平。脂联素水平升高与内皮血管舒张活性改善之间的关系表明血管效应与脂联素血症之间存在机制联系。
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