The Alteration of HDL in Patients with AMI Inhibited Angiogenesis by Blocking ERK1/2 Activation

Abstract

Objective. High-density lipoprotein (HDL) was found vasoprotective, but numbers of patients with acute myocardial infarction (AMI) have normal or even high levels of pathological HDL (pHDL). So, we investigate the mechanism of pHDL in AMI patients on angiogenesis. Methods. HDL with normal levels from healthy subjects (nHDL, control group, n = 20 ) and patients with AMI (pHDL, experimental groups, n = 30 ) were obtained by super high speed centrifugation. Then, effects of HDL on proliferation, migration, angiogenesis, and expression of ERK1/2 and its phosphorylation in human umbilical vein endothelial cells (HUVEC) with or without PD98059 (inhibitor of ERK1/2) preincubation were detected. Results. Compared with the control group (nHDL), HDL from the experimental group (pHDL) significantly inhibited the phosphorylation of ERK1/2, proliferation, migration, and angiogenesis of HUVEC ( P < 0.05 ), while these effects of HDL could substantially be blocked by preincubation of PD98059 ( P < 0.05 ). Conclusion. HDL in AMI patients affects angiogenesis by inhibiting ERK1/2 activation free from HDL levels.

Modulation of the Cellular microRNA Landscape: Contribution to the Protective Effects of High-Density Lipoproteins (HDL)

“…The mechanism by which this occurs remains unknown, although tissue-specific miR expression is an established concept [ 97 , 98 , 99 , 100 ]. However, it is clear that native HDL from healthy subjects can promote angiogenesis, while that derived from patients with coronary artery disease or diabetes attenuates this response [ 61 , 62 , 63 , 64 , 65 ]; native HDL suppresses miR-24-3p, and enhances vinculin expression, resulting in increased production of nitric oxide [ 188 , 189 ]. In contrast, dysfunctional HDL derived from CAD patients delivered miR-24-3p via SR-B1, inhibiting vinculin expression and NO production, and leading to superoxide production, while the overexpression of vinculin or inhibition of miR-24-3p reversed the impaired angiogenesis associated with dysfunctional HDL [ 189 ].…”

“…Treatment with HDL-like nanoparticles blocks MDSC in vitro and in vivo, reducing tumour size and metastatic tumour burden [ 60 ]. HDL also promotes angiogenesis [ 61 , 62 , 63 , 64 ] and wound healing [ 64 , 65 , 66 ] through the interaction of S1P with S1P3 receptor [ 61 ] and via interactions with SR-B1 and activation of the PI3K/Akt pathway. This increases the proliferation and migration of endothelial cells, and promotes re-epithelialization.…”