Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression.
Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression.
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DOI：
10.1371/journal.pone.0048530
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Pan B;Ma Y;Ren H;He Y;Wang Y;Lv X;Liu D;Ji L;Yu B;Wang Y;Chen YE;Pennathur S;Smith JD;Liu G;Zheng L
糖尿病HDL刺激内皮细胞（EC）增殖、迁移和粘附细胞外基质的能力减弱。这种功能障碍的机制知之甚少，因此，我们试图确定糖尿病HDL功能障碍的机制特征。我们发现，糖尿病HDL对人脐静脉内皮细胞（HUVECs）的功能障碍与HDL受体蛋白SR-BI的下调有关。正常HDL以双相方式诱导HUVECs中Akt磷酸化。虽然糖尿病HDL在20分钟后正常诱导Akt磷酸化，但在糖尿病HDL处理后24小时观察到的磷酸化减少。为了确定SR-BI下调对糖尿病HDL的EC反应减弱的作用，从野生型和SR-BI（-/-）小鼠中分离小鼠主动脉内皮细胞（MAEC），并用正常和糖尿病HDL处理。在SR-BI（−/−）细胞中，正常HDL对野生型MAEC的增殖和迁移作用大大减弱。与此相反，对糖尿病HDL的反应在两种类型中均受损，这表明糖尿病HDL对EC增殖和迁移的有效性降低可能是由于SR-BI的下调。此外，SR-BI下调降低了糖尿病HDL长期激活Akt的能力。糖尿病HDL在促进EC增殖、迁移和粘附基质方面功能失调，这与SR-BI的下调有关。此外，SR-BI下调降低了糖尿病HDL长期激活Akt的能力。
Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (−/−) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (−/−) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically.
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影响因子：
4.8
作者：
Kimura, T;Tomura, H;Okajima, F
通讯作者：
Okajima, F
影响因子：
20.3
作者：
Valiyaveettil, Manojkumar;Kar, Niladri;Podrez, Eugene A.
通讯作者：
Podrez, Eugene A.
影响因子：
37.8
作者：
Sorrentino, Sajoscha A.;Besler, Christian;Landmesser, Ulf
通讯作者：
Landmesser, Ulf
影响因子：
158.5
作者：
Barter, Philip;Gotto, Antonio M.;Fruchart, Jean-Charles
通讯作者：
Fruchart, Jean-Charles
DOI：
10.1161/01.atv.0000079011.67194.5a
发表时间：
2003-07-01
影响因子：
8.7
作者：
Kimura, T;Sato, K;Okajima, F
通讯作者：
Okajima, F