Essential role of HDL on endothelial progenitor cell proliferation with PI3K/Akt/cyclin D1 as the signal pathway
| Autor: | Hua Zhang, Qiu-hua Zhang, Peimao Liu, Mingpeng She, Hong-chao Yin |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Nitric Oxide Synthase Type III Angiogenesis Cellular differentiation Biology Endothelial progenitor cell General Biochemistry Genetics and Molecular Biology Phosphatidylinositol 3-Kinases Cyclin D1 Cell Movement Internal medicine medicine Animals Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Stem Cells Endothelial Cells Cell Differentiation Rats Cell biology Endocrinology embryonic structures cardiovascular system lipids (amino acids peptides and proteins) Lipoproteins HDL Wound healing Proto-Oncogene Proteins c-akt Signal Transduction circulatory and respiratory physiology Lipoprotein |
| Zdroj: | Experimental Biology and Medicine. 235:1082-1092 |
| ISSN: | 1535-3699 1535-3702 |
| DOI: | 10.1258/ebm.2010.010060 |
| Popis: | High-density lipoprotein (HDL) is known as an important factor in vascular wall remodeling that also affects gene expression in cell proliferation and differentiation. In this article, the role of HDL on endothelial progenitor cell (EPC) proliferation, angiogenesis and the signal pathway involved was studied, particularly the influence of HDL in strengthening the promoting effect of EPCs on wound healing of the arterial wall in hypercholesterolemic rats. Mononuclear cells isolated from rat bone marrow displayed characteristics of EPCs after cultivation. The role of HDL on EPC function and the signal pathway involved were studied by Western blotting, in vitro migration and ‘tube’ formation. Re-endothelialization and the number of circulating EPCs were compared between normal rats, hypercholesterolemic rats and hypercholesterolemic rats with HDL treatment. Results showed that HDL participated in the healing process by promoting EPC proliferation, migration and ‘tube’ formation. HDL activates cyclin D1 via phosphatidylinositol 3-kinase (PI3K)/Akt stimulation. Inhibition of PI3K/Akt via pharmacological or small interfering RNA approaches significantly attenuated HDL-induced EPC migration, proliferation and ‘tube’ formation. Results of experiments in vivo showed that HDL increased the number of circulating EPCs and promoted re-endothelialization in wound healing. These findings demonstrate for the first time that PI3K/Akt-dependent cyclin D1 activation plays an essential role in HDL-induced EPC proliferation, migration and angiogenesis. |
| Databáze: | OpenAIRE |
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