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Effects of Adiponectin on Proliferation and Differentiation of Endothelial Progenitor Cells and the Possible Mechanism

Author: YingZhiQiang
Tutor: XuGeng
School: Zhejiang University
Course: Clinical
Keywords: Endothelial progenitor cells Mononuclear cells Density gradient centrifugation Adiponectin receptors Adiponectin EPCs MAPK p38 JNK
CLC: R541.4
Type: PhD thesis
Year: 2009
Downloads: 303
Quote: 0
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Abstract


People's living standards improve, and some bad living and / or long-term existence diet, leading to obesity, impaired glucose tolerance, insulin resistance and type 2 diabetes increasing number of people, it has become a public health problem, causing endocrine, cardiovascular and cerebrovascular diseases, clinicians and public health researchers are highly valued. Clinical research and epidemiological investigations have confirmed that these metabolic diseases and cardiovascular diseases are closely related, metabolic syndrome and type 2 diabetes has been considered for coronary heart disease risk equivalent. Obesity caused by increased secretion of inflammatory cytokines lead to insulin resistance is an important factor, but also leading to endothelial cell damage and dysfunction of the reasons. Type 2 diabetes high blood sugar condition which is also on the vascular Neipi You microcirculation vascular endothelial cause damage, which increases atherosclerosis, coronary heart disease and other cardiovascular diseases and promote further development of lesions is very important. Adiponectin is secreted by adipose tissue, adipose-specific cytokines, and obesity, impaired glucose tolerance, insulin resistance and type 2 diabetes is closely related to people suffering from these diseases, plasma adiponectin levels were significantly decreased. Recent studies have shown that adiponectin by inhibiting the formation of foam cells, inhibition of apoptosis, reducing the generation and accumulation of inflammatory factors which play an anti-atherosclerotic lesions role. Functional status of vascular endothelial cells and the development of various cardiovascular diseases are closely related. In endothelial damage or high blood sugar and other factors stimulated endothelial function disorder. Compared with the normal population, suffering from high blood pressure, coronary heart disease and other cardiovascular diseases, people plasma adiponectin levels were significantly reduced. Currently, hypoadiponectinemia is considered to be an independent risk factor for coronary heart disease and a predictor of coronary heart disease severity with both closely related, therefore, be used as prognostic indicators. Endothelial progenitor cells (endothelial progenitor cells, EPCs) are a class can proliferate and differentiate into vascular endothelial cells precursor cells, not only involved in embryonic blood vessel formation, is also involved in postnatal angiogenesis and endothelial damage repair, which for the prevention of and treatment of various vascular damage associated with cardiovascular disease has important pathological and physiological significance. For EPCs in a variety of ischemic disease and trauma treatment of the body and how to effectively promote the proliferation and differentiation of EPCs is currently hot research field. It has been found in mouse hematopoietic stem cells (hematopoietic stem cells, HSCs) present on the surface of adiponectin receptors, adiponectin can promote the proliferation of HSCs in vivo and improve its functionality, is thought to be indispensable for growth factors. EPCs vascular endothelial precursor cells, both endothelial cells and progenitor cells, some biological properties. Whether EPCs express adiponectin receptors, adiponectin on the proliferation and differentiation of EPCs whether the impact is unclear. Based on the theoretical basis of the above, we propose hypothesis: adiponectin may affect the number and function of EPCs, thus affecting the ability to repair vascular endothelial injury, endothelial injury and maintain a dynamic balance between repair, and promote the recovery of endothelial function, thereby delaying artery atherosclerotic lesion development and progression. Therefore, the purpose of this experiment is to understand the existence of EPCs adiponectin receptor expression and adiponectin would not affect the proliferation and differentiation of EPCs, and explore its possible mechanism. The following sub-section 2 of the research methods, results and conclusions are briefly described. The first part of the progenitor cell isolation, culture, identification and adiponectin receptor expression Objective: cord blood EPCs were isolated, cultured and identified; investigate whether EPCs adiponectin receptor expression. Methods: Ficoll density gradient centrifugation from human umbilical cord blood mononuclear cells obtained, it was seeded in pre-coated with fibronectin culture plates, purified by adherence screening method using FITC-UEA-I and DiI-Ac -LDL double staining and flow cytometry EPCs surface markers (CD34, VEGFR-2 and AC133) to verify the isolation, culture resulting EPCs; via RT-PCR, Western blot and immunocytochemistry method of testing the existence of EPCs adiponectin receptor expression. Results: The cultured cells obtained 81.4 ± 11.7% of FITC-UEA-I and DiI-Ac-LDL staining double positive; using flow cytometry to detect the expression of VEGFR-2 (76.6 ± 7.0%), CD34 (42.9 ± 8.5 %), AC133 (19.8 ± 3.9%); adiponectin receptors AdipoR1 and AdipoR2 mRNA and protein were expressed on EPCs. Conclusions: 1 using density gradient centrifugation method for culturing adherent screening from human umbilical vein can successfully isolated and cultured EPCs. 2 EPCs were isolated and cultured in the presence of adiponectin receptors AdipoR1 and AdipoR2 expression. The second part of adiponectin on proliferation and differentiation of progenitor cells and its mechanism Objective: To observe adiponectin on isolated and cultured EPCs proliferation and differentiation and to explore its possible mechanism. Methods: EPCs isolated cultured 15-20 days, using MTT assay of adiponectin on EPCs proliferation. Real time PCR detection with vWF, CD31, CD34, AC133 evaluate the relative expression of adiponectin on EPCs differentiation. Western blot analysis with the role of adiponectin at different times after p-JNK, JNK, p-p38, p38, ERK, p-ERK expression, etc., and use the signal transduction inhibitors SB203580 and SP600125 validated intervention adiponectin on EPCs proliferation and differentiation may affect signal transduction pathway. Result: the role of adiponectin could make the number of EPCs (and MTT values) increases, 30μg/ml for 48h and the most obvious; adiponectin (30μg/ml) for 48h after the cells expressing vWF, CD31mRNA relative volumes have increase, while CD34, AC133 mRNA expression levels of a downward; adiponectin after 5min, EPCs can be detected phosphorylation of p38 and JNK, 30min peak, 60min decreased slightly, while the non-phosphorylated ERK (p-ERK ) expression. p38 signal transduction inhibitor SB203580 and JNK signal transduction inhibitor SP600125 blocked adiponectin can promote the role of p38 and JNK phosphorylation; SB203580 attenuates adiponectin proliferation effect; while SP600125 can weaken its differentiation-promoting EPCs effect. Conclusions: 1. Adiponectin can promote the proliferation and differentiation of EPCs, the role of a certain time and dose-dependent manner. 2.MAPK adiponectin pathway is involved in the proliferation and differentiation of human EPCs role in promoting.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)
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