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The Basic Research of the Impact of Hyperinsulinemia on Endothelial Progenitor Cells and the Relationship between Insulin Resistance and the Extent of Coronary Artery Disease

Author: QinQing
Tutor: QianJuYing；ShenZuo；SunAiJun
School: Fudan University
Course: Internal Medicine
Keywords: Endothelial progenitor cells Atherosclerosis Diabetes Nitric oxide synthase Insulin Insulin Resistance
CLC: R543.5
Type: Master's thesis
Year: 2008
Downloads: 171
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Abstract

(Atherosclerosis, AS) and associated clinical consequences of atherosclerosis, such as coronary heart disease, the number one killer has become a threat to human health in today's society. At present, more and more evidence is the arteriosclerosis occurred mainly due to endothelial damage caused by multiple risk factors and endothelial functional imbalance between the self-repair. The view of the past that the the injured endothelial repair by neighboring endothelial cell migration and proliferation, but recent studies have found that bone marrow-derived endothelial progenitor cells (EPCs) are a group of proliferation and differentiation potential of the cells of mature endothelial cells bear the repair vascular the task. The study found that the variety caused by atherosclerosis risk factors (such as hypercholesterolemia, hypertension, high cystine hyperlipidemia, high-sugar, etc.) can make the number and function of EPCs significantly reduced, suggesting that EPCs occurrence of AS and development plays an important role. Characterized by insulin resistance (IR) and hyperinsulinemia diseases such as diabetes, obesity, decreased glucose tolerance, lipid metabolism disorders are an important part of the cardiovascular system imbalance by causing endothelial dysfunction, leading to high blood pressure , atherosclerosis and coronary artery disease. IR can cause endothelial dysfunction through different mechanisms. Type 2 diabetes, metabolic syndrome and insulin resistance in healthy volunteers the number and function of EPCs are decreased speculate that IR the EPCs has the inhibition, but IR EPCs direct role is unclear. In this study, first of all in vitro intervention factor for the high concentration of insulin observed in endothelial progenitor cells of endothelial nitric oxide synthase (eNOS) expression of human umbilical cord blood culture. Contemplated by comparing clinical diagnosis of stable angina, non-diabetic patients with insulin resistant and non-insulin-resisters number of EPCs and functional differences exist, to explore the impact of the IR on EPCs in specific populations. Finally, by studying the clinical suspected as the relationship between insulin resistance in non-diabetic patients of stable angina degree of coronary artery lesions, to explore the role of IR in the development of coronary heart disease. In this study, from the perspective of the cellular level and clinical epidemiology research EPCs IR state change and its role in the pathogenesis of AS, the text consists of three parts. Affect the purpose of the first part of the high concentrations of insulin on cultured endothelial progenitor cells eNoS expression: hyperinsulinemia performance of a compensatory or treatment of insulin resistance performance, many studies have confirmed hyperinsulinemia athero sclerosis (AS) an independent risk factor for hyperinsulinemia cause the AS mechanism is not clear. The bone marrow-derived endothelial progenitor cells (EPCs) are a group of proliferation, differentiation potential of the cells of mature endothelial cells involved in the repair of vascular injury. This paper aims vitro studies high concentrations of insulin on EPCs expression of endothelial nitric oxide synthase (eNOS) Influence of hyperinsulinemia caused by the mechanism of the AS. Methods: density gradient centrifugation from umbilical cord blood (about 80-90ml / bag), mononuclear cells were isolated (approximately 10 ~ 6-10 ~ 7), vascular endothelial growth factor (VEGF) stimulated cultured for 7 days, EPCs to form a typical colony and Dil-acLDL (Dil-labeled acetylated low-density lipoprotein) identified as being differentiated EPCs. In each of culture wells (cell is about 10 ~ 4-10 ~ 5 / well) were added to a final concentration of 0,1 nM, 10 nM, 100 nM, 1000nM insulin for 24 hours, using Trizol reagent extraction of total cellular RNA by RT -PCR to detect expression of eNOS mRNA. Results: eNOS expression began to increase since 1nM, 10 nM highest expression, 100nM began to weaken, suggesting that the physiological concentration of insulin (1nM) play a catalytic role in the expression of eNOS and 10 times higher than the physiological concentration (10nM) continued to show to promote the role of high concentration insulin inhibition (> 10nM). Conclusion: within a certain range, higher than the physiological concentration of insulin on EPCs function with the promotion, but excessive concentrations of insulin EPCs can dampen demand. Prompt with increased insulin resistance, EPCs dysfunction caused due to high insulin may have an adverse impact on the formation of atherosclerosis. The purpose of the second part of stable angina pectoris number of circulating endothelial progenitor cells in patients with insulin resistance and its function: the disease is characterized by insulin resistance, such as diabetes, obesity, impaired glucose tolerance decreased, lipid metabolism disorders are cardiovascular system function imbalances The important part of the cause endothelial dysfunction, which leads to high blood pressure, atherosclerosis and coronary heart disease. Recent studies from the coronary artery disease because of the imbalance in the endothelial cell injury and repair mechanisms. Endothelial progenitor cells (EPCs) derived from bone marrow, can differentiate into mature endothelial cells endothelial regeneration participate in endothelial repair. This study selected non-diabetic patients with stable angina pectoris as the object of study designed to observe the relationship between insulin resistance and endothelial progenitor cell number and function. Methods: clinical suspected stable angina underwent coronary angiography 27 patients, 19 were male, the average age of 58 ± 7 years of age, fasting blood insulin and blood lipids, blood glucose and other biochemical parameters, using the the McAuley index for assessing the degree of insulin resistance, according to McAuley index <5.8 and McAuley index ≥ 5.8 is divided into insulin resistance group (13 cases), non-insulin-resistant group (14 cases), using the the coronary lesions integral evaluation of coronary artery stenosis. Peripheral blood the 100μl line EPCs streaming count (markers CD133 and VEGFR-2), peripheral blood 12ml by density gradient centrifugation was underwent in vitro cultures of mononuclear cells, 7 days after the counting endothelial progenitor cell colony-forming units. Results: insulin resistance in patients with pathological score than non-insulin resistance group (2.34 ± 2.73 vs 0.68 ± 0.82.p <0.05), blood HDL-c levels compared with non-insulin resistance group (1.08 ± 0.17 mmol / L ratio of 1.30 ± 0.32 mmol / L, p <0.05). Insulin resistance group, the number of endothelial progenitor cells (0.035 ± 0.046% vs 0.116 ± 0.112%, p <0.05) and colony forming units (54.9 ± 28.9 vs 75.2 ± 20.7.p <0.05) compared with non-insulin resistance group. Conclusion: insulin resistance, stable angina pectoris patients circulating endothelial progenitor cell numbers and function were lower, more severe coronary artery stenosis the prompt endothelial progenitor cell dysfunction may cause atherosclerosis one of the mechanisms of insulin resistance. The purpose of the relationship of insulin resistance and the severity of coronary lesions in patients with stable angina pectoris in the third part: the current study found that insulin resistance may cause endothelial dysfunction, thereby contributing to atherosclerosis, insulin resistance is an independent risk factor for coronary heart disease. This study selected clinically diagnosed as combined insulin resistance in non-diabetic patients with stable angina pectoris as the research object, intended to study the degree of insulin resistance and coronary artery lesions relationship. Methods: suspected stable angina hospitalized cases, 272 cases of coronary angiography, 199 cases of men with an average age of 59 ± 8 years old, except for patients with diabetes, fasting blood insulin and blood lipids, blood glucose and other biochemical markers McAuley index evaluation insulin The degree of resistance (McAuley index <5.8 for insulin resistance, McAuley's index ≥ 5.8 for non-insulin resistance), the evaluation of coronary artery stenosis according to coronary artery score. Results: Selected cases insulin resistant 85 cases (31.25%), 76 patients with coronary no atherosclerotic change (27.94%), 78 cases of coronary atherosclerotic plaque stenosis <50% (representing 28.68%), 118 cases of coronary artery stenosis ≥ 50% (43.3%). McAuley index with coronary artery score was negatively correlated (R = -0.153, p <0.05), fasting insulin concentration and coronary artery score correlation was statistically significant (p> 0.05). According to the coronary lesions integral packet (coronary artery score <1.89,1.9-4.83 ≥ 4.84 were divided into 3 groups), the coronary artery score high group the McAuley index lower (p <0.05). Fasting plasma insulin concentration in each group, the difference was not statistically significant. Conclusions: The severity of the degree of insulin resistance and coronary artery lesions was positively correlated with fasting insulin concentration and the severity of coronary lesions not related.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Vascular disease > Artery disease
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