Thiazolidinedione-independent activation of peroxisome proliferator-activated receptor γ is a potential target for diabetic macrovascular complications.
Thiazolidinedione-independent activation of peroxisome proliferator-activated receptor γ is a potential target for diabetic macrovascular complications.
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DOI：
10.1111/j.2040-1124.2011.00182.x
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发表时间：
2012-02-20
影响因子：
3.2
通讯作者：
Araki E
中科院分区：
文献类型：
--
作者：
Matsumura T;Taketa K;Shimoda S;Araki E
大血管并发症是糖尿病患者高发病率和高死亡率的原因。过氧化物酶体增殖物激活受体γ (PPARγ)在脂肪细胞分化和胰岛素增敏过程中起核心作用，也具有抗动脉粥样硬化作用。最近，一些他汀类药物、血管紧张素II型受体阻滞剂和钙通道阻滞剂被报道可以激活PPARγ。然而，PPARγ活化对糖尿病大血管并发症的影响尚不完全清楚。据报道，在动脉粥样硬化动物模型和临床研究中，噻唑烷二酮活化PPARγ可诱导血管细胞（包括单核/巨噬细胞、内皮细胞和平滑肌细胞）抗动脉粥样硬化作用。我们已经报道了用于治疗高胆固醇血症的羟甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）可以激活巨噬细胞中的PPARγ并通过激活PPARγ介导抗动脉粥样硬化作用。此外，替米沙坦，一种血管紧张素I型受体阻滞剂，已被报道通过激活PPARγ具有抗动脉粥样硬化作用。此外，我们报道了硝苯地平，一种二氢吡啶钙通道阻滞剂，可以激活PPARγ，从而介导巨噬细胞的抗动脉粥样硬化作用。因此，他汀类药物治疗和部分降压治疗可能通过激活PPARγ对高胆固醇血症和/或高血压合并糖尿病患者产生有益作用，并且PPARγ可能是糖尿病大血管并发症的治疗靶点。在本综述中，我们将重点关注PPARγ的抗动脉粥样硬化作用，并提出预防糖尿病大血管并发症的潜在治疗方法。糖尿病投资杂志，doi: 10.1111/ J .2040‐1124.2011.00182。x, 2012)
Macrovascular complications are responsible for the high morbidity and mortality in patients with diabetes. Peroxisome proliferator‐activated receptor γ (PPARγ) plays a central role in the process of adipocyte differentiation and insulin sensitization, and also possesses anti‐atherogenic effects. Recently, some statins, angiotensin II type 1 receptor blockers and calcium channel blockers have been reported to activate PPARγ. However, the impact of PPARγ activation on diabetic macrovascular complications is not fully understood. It has been reported that the activation of PPARγ by thiazolidinediones induces anti‐atherogenic effects in vascular cells, including monocytes/macrophages, endothelial cells and smooth muscle cells, in atherosclerotic animal models and in clinical studies. We have reported that hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which are used for treatment of hypercholesterolemia, activate PPARγ and mediate anti‐atherogenic effects through PPARγ activation in macrophages. Also, telmisartan, an angiotensin type I receptor blocker, has been reported to have anti‐atherogenic effects through PPARγ activation. Furthermore, we have reported that nifedipine, a dihydropyridine calcium channel blocker, can activate PPARγ, thereby mediating anti‐atherogenic effects in macrophages. Therefore, statin therapy and part of anti‐hypertensive therapy might produce beneficial effects through PPARγ activation in hypercholesterolemic and/or hypertensive patients with diabetes, and PPARγ might be a therapeutic target for diabetic macrovascular complications. In the present review, we focus on the anti‐atherogenic effects of PPARγ and suggest potential therapeutic approaches to prevent diabetic macrovascular complications. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00182.x, 2012)
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