FACTORS RESPONSIBLE FOR IMPAIRED FIBRINOLYSIS IN OBESE SUBJECTS AND NIDDM PATIENTS
FACTORS RESPONSIBLE FOR IMPAIRED FIBRINOLYSIS IN OBESE SUBJECTS AND NIDDM PATIENTS
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DOI：
10.2337/diabetes.43.1.104
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发表时间：
1994-01-01
期刊：
影响因子：
7.7
通讯作者：
SOBEL, BE
中科院分区：
文献类型：
--
作者：
MCGILL, JB;SCHNEIDER, DJ;SOBEL, BE
加速动脉粥样硬化是非胰岛素依赖型糖尿病 (NIDDM) 患者死亡的主要原因。内源性纤溶活性受损可能会使血管腔壁表面暴露于持续和复发的血栓和凝块相关丝裂原，从而加速动脉粥样硬化。本研究的目的是进一步表征瘦和肥胖的非糖尿病受试者以及 NIDDM 患者的内源性纤维蛋白溶解，并确定造成所确定改变的机制。与瘦对照受试者相比，肥胖和糖尿病受试者的 1 型纤溶酶原激活剂抑制剂 (PAI-1) 血浆浓度升高了三倍。尽管肥胖和糖尿病受试者的组织型纤溶酶原激活剂血浆浓度没有显着差异，但基础内源性纤溶活性和刺激性内源性纤溶活性均降低。这种下降与血浆中 PAI-1 活性的增加有关，进而与免疫反应性胰岛素和 C 肽浓度的增加有关。这些结果与我们之前的观察结果一致，即胰岛素及其前体对体外 PAI-1 细胞表达的直接刺激作用，以及其他人的观察结果，表明 NIDDM 患者基础纤溶活性降低。内源性纤溶活性受损可能导致血管壁管腔表面长期或反复暴露于微血栓和凝块相关丝裂原，这可能会加速高胰岛素血症受试者的动脉粥样硬化。
Accelerated atherosclerosis is the leading cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM). Impaired endogenous fibrinolytic activity may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi and clot-associated mitogens. This study was conducted to further characterize endogenous fibrinolysis in lean and obese nondiabetic subjects and in NIDDM patients and to identify mechanisms responsible for the alterations identified. Obese and diabetic subjects had threefold elevations of plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) compared with values in lean control subjects. Despite the lack of significant differences in plasma concentrations of tissue-type plasminogen activator in the obese and diabetic subjects, both basal and stimulated endogenous fibrinolytic activities were decreased. The decreases were associated with increased activity of PAI-1 in plasma, in turn correlated with increased concentrations of immunoreactive insulin and C-peptide. These results are consistent with our previous observations demonstrating direct stimulatory effects of insulin and its precursors on cellular expression of PAI-1 in vitro and observations by others demonstrating decreased basal fibrinolytic activity in NIDDM patients. Impaired endogenous fibrinolytic activity could lead to prolonged or recurrent exposure of luminal surfaces of vessel walls to microthrombi and clot-associated mitogens that may accelerate atherosclerosis in hyperinsulinemic subjects.