OX-HDL: A Starring Role in Cardiorenal Syndrome and the Effects of Heme Oxygenase-1 Intervention

Abstract

In this review, we will evaluate how high-density lipoprotein (HDL) and the reverse cholesterol transport (RCT) pathway are critical for proper cardiovascular–renal physiology. We will begin by reviewing the basic concepts of HDL cholesterol synthesis and pathway regulation, followed by cardiorenal syndrome (CRS) pathophysiology. After explaining how the HDL and RCT pathways become dysfunctional through oxidative processes, we will elaborate on the potential role of HDL dysfunction in CRS. We will then present findings on how HDL function and the inducible antioxidant gene heme oxygenase-1 (HO-1) are interconnected and how induction of HO-1 is protective against HDL dysfunction and important for the proper functioning of the cardiovascular–renal system. This will substantiate the proposal of HO-1 as a novel therapeutic target to prevent HDL dysfunction and, consequently, cardiovascular disease, renal dysfunction, and the onset of CRS.

HDL Composition, Heart Failure, and Its Comorbidities

“…We propose that various post-translational modifications (for example, MPO adducts) might alter specific ox-HDL characteristics (for example, higher vs. lower affinity toward SR-BI); nonetheless, renal dysfunction can contribute toward "dysfunctional" HDL particles. Moreover, ox-HDL exhibits diminished endothelial nitric oxide synthase (eNOS) mediated endothelial protective function as well as anti-apoptotic activity, which leads to impaired endothelial repair and increased proinflammatory activation (84)(85)(86).…”

Subpopulations of High-Density Lipoprotein: Friends or Foes in Cardiovascular Disease Risk in Chronic Kidney Disease?

“…The pathophysiological mechanism for cardiorenal syndrome has not been completely established, but in all its types, oxidative stress and inflammation appear to play an important role [ 93 ]. Given the high prevalence of CVD and CKD, the potential interest of several biomarkers for cardiorenal syndrome, pertinent for both conditions, has been investigated and a few renocardiovascular biomarkers have emerged.…”

“…Given the high prevalence of CVD and CKD, the potential interest of several biomarkers for cardiorenal syndrome, pertinent for both conditions, has been investigated and a few renocardiovascular biomarkers have emerged. HDL alterations and dysfunction have been suggested to contribute to increase cardiorenal syndrome risk [ 93 ]. Oxidation of HDL (oxHDL) has been pointed to as a cause for dysfunctional HDL and as one potential renocardiovascular biomarker [ 93 ].…”

“…HDL alterations and dysfunction have been suggested to contribute to increase cardiorenal syndrome risk [ 93 ]. Oxidation of HDL (oxHDL) has been pointed to as a cause for dysfunctional HDL and as one potential renocardiovascular biomarker [ 93 ].…”

The Association of Nephroblastoma Overexpressed (NOV) and Endothelial Progenitor Cells with Oxidative Stress in Obstructive Sleep Apnea

“…White adipose tissue has higher NOV levels than beige and brown adipose tissue [15]. In addition, the inflammatory state is destructive to mitochondria and contributes to multiorgan dysfunction [30][31][32]. The ability to generate thermogenesis via mitochondrial electron transport chain (ETC) uncoupling is highest in brown fat, followed by beige, and finally least in white fat [19,20].…”