Abstract
The HDL hypothesis stating that simply raising HDL cholesterol (HDL-C) may produce cardiovascular benefits has been questioned recently based on several randomized clinical trials using CETP inhibitors or niacin to raise HDL-C levels. However, extensive pre-clinical data support the vascular protective effects of administration of exogenous ApoA-1 containing preβ-HDL like particles. Several small proof-of-concept clinical trials using such HDL/ApoA-1 infusion therapy have shown encouraging results but definitive proof of efficacy must await large scale clinical trials. In addition to HDL infusion therapy an alternative way to exploit beneficial cardiovascular effects of HDL/ApoA-1 is to use gene transfer. Preclinical studies have shown evidence of benefit using this approach; however clinical validation is yet lacking. This review summarizes our current knowledge of the aforementioned strategies.
Highlights
Purified wild type ApoA-I from human plasma complexed with phosphatidylcholine
In this study we demonstrated substantially superior athero-protective effects of ApoA-1Milano gene transfer compared to wild type ApoA-1 gene transfer supporting the possible gain of function nature of the Milano mutation
We have recently shown that a single intravenous injection of AAV8 encoding ApoA-1Milano gene produces significant inhibition of atherosclerosis progression in hyperlipidemic mice (Tian et al, 2015)
Summary
Coronary atherosclerotic plaque regression in the treatment group Purified wild type ApoA-I from human plasma complexed with phosphatidylcholine Reduction of VCAM-1 expression and lipid content in the plaque; increase in HDL-C level and capacity of cholesterol efflux
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