Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration
Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration
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DOI：
10.1067/mva.2001.111806
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发表时间：
2001-03-01
影响因子：
4.3
通讯作者：
LoGerfo, FW
中科院分区：
文献类型：
--
作者：
Faries, PL;Rohan, DI;LoGerfo, FW
目的：与非糖尿病患者相比，糖尿病患者经历进行性大血管动脉粥样硬化和内膜超塑性再狭窄的频率增加。这些观察结果表明，血管平滑肌细胞（VSMCs）在糖尿病患者中表现出表型上的不同和更具侵略性的方式。在这项研究中，我们比较了从糖尿病和非糖尿病患者获得的人VSMCs的体外增殖、粘附和迁移率。方法：从23例下肢广泛动脉粥样硬化的糖尿病患者（9条动脉、14条静脉）和15例非糖尿病患者（9条动脉、6条静脉）中分离VSMC培养物。所有患者年龄在61 ~ 78岁之间（糖尿病患者平均68.4岁，非糖尿病患者平均67.3岁）。所有糖尿病患者均为2型糖尿病。血管标本取自截肢时的细静脉和隐静脉的动脉血运重建术。用总DNA荧光光度法测定第2代和第3代细胞的增殖能力，用改良的Boyden室测定细胞的粘附和迁移能力。结果：糖尿病患者的平均病程为11.6±4.1年。糖尿病并发症（视网膜病变、神经病变、肾病、冠状动脉病变）的平均数量为每位患者2.8±0.7例。糖尿病VSMCs在细胞培养中表现出异常形态，失去了正常的山谷结构。与非糖尿病来源的VSMCs（116 +/- 42吸收单位）相比，糖尿病来源的VSMCs（156 +/- 57吸收单位）的增殖显著增加（P < 0.001）。糖尿病VSMCs的粘附率（高倍视场63.6 +/- 24 vs高倍视场37.9 +/- 13,P = 0.002）和迁移率（低倍视场397 +/- 151 vs低倍视场121 +/- 99，P = 0.001）显著提高。结论糖尿病VSMCs的增殖、粘附和迁移率显著增加，细胞培养形态异常提示接触抑制异常。这些对培养的人类VSMCs的观察结果与糖尿病患者临床观察到的缺血性动脉粥样硬化发生率增加和再狭窄发生率增加相一致。促进动脉粥样硬化和内膜增生的行为似乎是DM-VSMC表型固有的，在设计限制糖尿病患者动脉粥样硬化和内膜增生的方法时必须考虑到这一点。
Purpose: Patients with diabetes methods (DM) experience progressive macrovascular atherosclerosis and intimal hyper plastic restenosis with increased frequency as compared with nondiabetic patients. These observations suggest that vascular smooth muscle cells (VSMCs) behave in a phenotypically different and more aggressive manner in diabetic patients. In this study, we compared the in vitro rates of proliferation, adhesion, and migration of human VSMCs obtained from diabetic and nondiabetic patients.Methods: Human VSMC cultures were isolated from 23 diabetic patients (9 artery, 14 vein) and 15 nondiabetic patients (9 artery, 6 vein) with extensive lower extremity atherosclerosis. All patients were between 61 and 78 years of age (average: 68.4 years [diabetic]; 67.3 years [nondiabetic]). All diabetic patients had type 2 DM. Vascular specimens were obtained at the time of amputation from infragenicular arteries and during arterial revascularization from saphenous veins. Cells from passages 2 and 3 were assayed for their proliferative capacity with total DNA fluorescence photometry and for adhesion and migration with a modified Boyden chamber.Results: The average duration of diabetes was 11.6 +/- 4.1 years. The average number of diabetic complications (retinopathy, neuropathy, nephropathy, coronary artery disease) was 2.8 +/- 0.7 per patient. Diabetic VSMCs exhibited abnormal morphology in cell culture with loss of the normal hill and valley configuration. Proliferation was significantly increased in VSMCs of diabetic origin (156 +/- 57 absorption units) as compared with those of nondiabetic origin (116 +/- 42 absorption units) (P < .001). Diabetic VSMCs demonstrated significantly greater adhesion (63.6 +/- 24 per high-power field vs 37.9 +/- 13 per high-power field; P = .002) and migration (397 +/- 151 per low-power field vs 121 +/- 99 per low-power field; P = .001) rates.Conclusions Diabetic VSMCs exhibit significantly increased rates of proliferation, adhesion, and migration as well as abnormal cell culture morphology suggestive of abnormal contact inhibition. These observations of human VSMCs in culture are consistent with ther increased rate of infragenicular atherosclerosis and the increased rates of restenosis observed clinically in diabetic patients. The atherosclerosis- and intimal hyperplasia-promoting behavior exhibited appears to be intrinsic to the DM-VSMC phenotype and must be considered when designing methods to limit atherosclerosis and intimal hyperplasia in diabetic patients.