Abstract
The impact of high-density lipoprotein (HDL) cholesterol on the development of atherosclerosis and diseases of systemic circulation has been well documented both in experimental and registry studies. Recent discoveries in pulmonary arterial hypertension (PAH) revealed a significant impact of HDL on pulmonary artery vasoreactivity and patients’ prognosis. The vasoprotective activity of HDL primarily involves vascular endothelium that also plays a central role in pulmonary arterial hypertension (PAH) pathobiology. However, the exact mechanism in which this lipoprotein fraction exerts its effect in pulmonary circulation is still under investigation. This paper reviews potential vasoprotective mechanisms of HDL in pulmonary circulation and presents current clinical reports on the role of HDL in PAH patients.
Highlights
The significance of plasma high-density lipoprotein (HDL) cholesterol concentration in the development and progression of diseases has been documented by reports from both experimental and observational studies
It was supported by a series of animal studies showing inhibition of atherosclerosis in cholesterol-fed rabbits after HDL infusion [2] and in transgenic mice overexpressing apolipoprotein A-I [3], which is the major protein component of HDL particles
The recent meta-analysis with the Mendelian randomization approach showed that increased HDL associated with cholesteryl ester transfer protein (CETP) gene polymorphism cannot be translated into reduction of cardiovascular risk [19]
Summary
The significance of plasma high-density lipoprotein (HDL) cholesterol concentration in the development and progression of diseases has been documented by reports from both experimental and observational studies. The strong inverse relationship between HDL and cardiovascular disease was first established by the Framingham Heart Study [1] This observation led to the hypothesis that HDL cholesterol might demonstrate protective properties against coronary artery disease. Despite the previous reports suggesting benefits of increasing HDL concentration with nicotinic acid [12], current trials with extended-release niacin as an add-on therapy to the background statin failed to reduce the risk of cardiovascular events [13,14]. In the dal-ACUTE study with dalcetrapib, authors have shown the dissociation between an increase of HDL levels and improvements in HDL function [20] This highlighted the importance of HDL function in cardiovascular protection, which cannot be accurately estimated only by measuring lipoprotein concentration [21,22]
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