HDL Composition, Heart Failure, and Its Comorbidities.

Ahmed Diab,Zhen Guo,Ali Javaheri,Carla Valenzuela Ripoll

doi:10.3389/fcvm.2022.846990

HDL Composition, Heart Failure, and Its Comorbidities.

Ahmed Diab, Zhen Guo + Show 2 more

Open Access

https://doi.org/10.3389/fcvm.2022.846990

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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.

Highlights

Cardiovascular disease (CVD) is a leading cause of mortality worldwide [1]
A clinical trial showed that reconstituted high-density lipoprotein (HDL) infusion shortens cardiac repolarization, demonstrating the capability of HDL to alter cardiac electrophysiological properties [16]
We propose that various post-translational modifications might alter specific Oxidized HDL (ox-HDL) characteristics; renal dysfunction can contribute toward “dysfunctional” HDL particles

Summary

Introduction

Cardiovascular disease (CVD) is a leading cause of mortality worldwide [1]. Heart failure (HF) is a common result of cardiometabolic disease and a major contributor to CVD mortality [2]. In HF patients, plasma cholesterol concentrations are inversely associated with mortality [6, 7]. This observation, termed the “cholesterol paradox,” could be related to malnutrition, cachexia [8, 9], and inflammation [10–14] observed in HF patients, as well as direct effects of lipoproteins on the myocardium. A clinical trial showed that reconstituted high-density lipoprotein (HDL) infusion shortens cardiac repolarization, demonstrating the capability of HDL to alter cardiac electrophysiological properties [16]. Both studies exemplify a direct role of lipoproteins on the myocardium. Lipoproteins can function as a fuel source, an important consideration in HF patients, where the energy-starved myocardium primarily consumes ketone bodies and fatty acids [17]

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Conclusion