过氧化物酶体增殖物激活受体-γ 作为心血管疾病的治疗靶点：证据与不确定性。
PPAR-γ as a therapeutic target in cardiovascular disease: evidence and uncertainty.
机构信息
Cardiology Section, Denver VA Medical Center, US Department of Veterans Affairs, Denver, CO, USA.
出版信息
J Lipid Res. 2012 Sep;53(9):1738-54. doi: 10.1194/jlr.R024505. Epub 2012 Jun 8.
Abstract
Peroxisome proliferator-activated receptor γ (PPAR-γ) is a key regulator of fatty acid metabolism, promoting its storage in adipose tissue and reducing circulating concentrations of free fatty acids. Activation of PPAR-γ has favorable effects on measures of adipocyte function, insulin sensitivity, lipoprotein metabolism, and vascular structure and function. Despite these effects, clinical trials of thiazolidinedione PPAR-γ activators have not provided conclusive evidence that they reduce cardiovascular morbidity and mortality. The apparent disparity between effects on laboratory measurements and clinical outcomes may be related to limitations of clinical trials, adverse effects of PPAR-γ activation, or off-target effects of thiazolidinedione agents. This review addresses these issues from a clinician's perspective and highlights several ongoing clinical trials that may help to clarify the therapeutic role of PPAR-γ activators in cardiovascular disease.
摘要
过氧化物酶体增殖物激活受体 γ（PPAR-γ）是脂肪酸代谢的关键调节因子，促进其在脂肪组织中的储存，并降低游离脂肪酸的循环浓度。PPAR-γ 的激活对脂肪细胞功能、胰岛素敏感性、脂蛋白代谢以及血管结构和功能的测量指标有有利影响。尽管有这些作用，但噻唑烷二酮类 PPAR-γ 激活剂的临床试验并未提供确凿证据表明它们可降低心血管发病率和死亡率。实验室测量结果和临床结局之间的明显差异可能与临床试验的局限性、PPAR-γ 激活的不良反应或噻唑烷二酮类药物的脱靶效应有关。本综述从临床医生的角度探讨了这些问题，并强调了几项正在进行的临床试验，这些试验可能有助于阐明 PPAR-γ 激活剂在心血管疾病中的治疗作用。
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