HDL Composition, Heart Failure, and Its Comorbidities

Abstract

Although research on high-density lipoprotein (HDL) has historically focused on atherosclerotic coronary disease, there exists untapped potential of HDL biology for the treatment of heart failure. Anti-oxidant, anti-inflammatory, and endothelial protective properties of HDL could impact heart failure pathogenesis. HDL-associated proteins such as apolipoprotein A-I and M may have significant therapeutic effects on the myocardium, in part by modulating signal transduction pathways and sphingosine-1-phosphate biology. Furthermore, because heart failure is a complex syndrome characterized by multiple comorbidities, there are complex interactions between heart failure, its comorbidities, and lipoprotein homeostatic mechanisms. In this review, we will discuss the effects of heart failure and associated comorbidities on HDL, explore potential cardioprotective properties of HDL, and review novel HDL therapeutic targets in heart failure.

Keywords: apolipoprotein A-I; apolipoprotein M; cardiomyopathy; heart failure; high-density lipoprotein (HDL); sphingosine-1-phosphate.

Figure 1

Apolipoproteins role in heart failure progression. Heart failure causes reduced cardiac index and increased filling pressures, which subsequently leads to hepatic injury that can affect apolipoprotein production. In addition, heart failure-induced kidney injury may increase renal excretion of apolipoprotein M (ApoM). Co-morbidities such as diabetes and obesity are also known to reduce circulating apolipoproteins, contributing to inflammation, thus exacerbating kidney and hepatic injury, and provoking further cardiac dysfunction.

Figure 2

Apolipoprotein-dependent signal transduction pathways (A) Apolipoprotein A-I (ApoA-I) is the major component of high-density lipoproteins (HDL), and it binds scavenger receptor class B type I (SR-BI), which mediates selective uptake of cholesterol. SR-BI may also stabilize HDL particles allowing access to S1P receptors or activate other signaling cascades. (B) HDL and apolipoprotein M (ApoM)-dependent activation of S1P receptors (S1PR) leads to downstream G-protein coupled receptor signaling in both endothelial cells and cardiomyocytes. This signaling promotes diverse physiological responses including maintenance of endothelial barrier integrity, promotion of cell survival, and anti-inflammatory effects. Modified from (–242).