Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARgamma stimulation.
Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARgamma stimulation.
复制标题
DOI：
10.1186/1475-2840-8-49
复制
发表时间：
2009-09-08
影响因子：
9.3
通讯作者：
Flex A
中科院分区：
文献类型：
--
作者：
Biscetti F;Straface G;Arena V;Stigliano E;Pecorini G;Rizzo P;De Angelis G;Iuliano L;Ghirlanda G;Flex A
2 型糖尿病 (T2DM) 通常与微血管和大血管并发症相关，血糖控制与血管并发症的发生和进展之间存在很强的相关性。吡格列酮是一种过氧化物酶体增殖物激活受体-γ (PPARγ) 配体，适用于治疗 T2DM 型，可诱导血管效应，而这种效应似乎与血糖降低无关。通过使用后肢缺血小鼠模型，在本研究中我们发现吡格列酮可以恢复糖尿病小鼠缺血肌肉的血流恢复和毛细血管密度，并且该过程与血管内皮生长因子（VEGF）表达增加有关。重要的是，当内源性 Akt 受到抑制时，这些有益作用就会消失。此外，PPARγ及其选择性激动剂GW1929的直接激活不会恢复血流恢复和毛细血管密度。最后，通过吡格列酮和选择性 PPARγ 抑制剂 GW9662 的联合治疗，获得了重要的侧支血管生长。这些数据表明，Akt-VEGF 途径对于吡格列酮缺血诱导的血管生成作用至关重要，并且吡格列酮通过 PPARγ 独立方式发挥这种作用。
Type 2 diabetes mellitus (T2DM) is commonly associated with both microvascular and macrovascular complications and a strong correlation exists between glycaemic control and the incidence and progression of vascular complications. Pioglitazone, a Peroxisome proliferator-activated receptor-γ (PPARγ) ligand indicated for therapy of type T2DM, induces vascular effects that seem to occur independently of glucose lowering. By using a hindlimb ischemia murine model, in this study we have found that pioglitazone restores the blood flow recovery and capillary density in ischemic muscle of diabetic mice and that this process is associated with increased expression of Vascular Endothelial Growth Factor (VEGF). Importantly, these beneficial effects are abrogated when endogenous Akt is inhibited; furthermore, the direct activation of PPARγ, with its selective agonist GW1929, does not restore blood flow recovery and capillary density. Finally, an important collateral vessel growth is obtained with combined treatment with pioglitazone and selective PPARγ inhibitor GW9662. These data demonstrate that Akt-VEGF pathway is essential for ischemia-induced angiogenic effect of pioglitazone and that pioglitazone exerts this effect via a PPARγ independent manner.
登录
查看更多内容
影响因子：
5.3
作者：
Gensch, Christoph;Clever, Yvonne P.;Laufs, Ulrich
通讯作者：
Laufs, Ulrich
影响因子：
15.9
作者：
HALVORSEN, YDC;BURSELL, SE;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
DOI：
10.1016/j.bbrc.2005.06.055
发表时间：
2005-08-19
影响因子：
3.1
作者：
Liu, HB;Hu, YS;Dear, AE
通讯作者：
Dear, AE
影响因子：
24.5
作者：
Galli, A;Ceni, E;Casini, A
通讯作者：
Casini, A
影响因子：
2.9
作者：
Chu, Kon;Lee, Soon-Tae;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu