Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis

Publisher Website
Google Scholar
Abstract
Background— Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model. Methods and Results— Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow–derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 μg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation w... Reconstituted HDL (rHDL) augmented angiogenesis in ischemic hindlimb with enhanced incorporation of bone marrow–derived cells in new vessels. rHDL promoted differentiation of endothelial progenitor cells via PI3K/Akt pathway. The beneficial effect of rHDL was abrogated in eNOS-deficient mice. rHDL might be useful in therapeutic angiogenesis.