The Critical Role of the Adipocytokine NOV in Obstructive Sleep Apnea Induced Cardiometabolic Dysfunction: A Review

Abstract

Obstructive sleep apnea (OSA) is highly prevalent and associated with oxidative stress, chronic inflammation, and adverse cardiovascular consequences. The comorbid condition of obesity remains epidemic. Both obesity and OSA are highly comorbid in patients with cardiovascular disease including atrial fibrillation, resistant hypertension, congestive heart failure, and coronary artery disease. Patients with these preexisting cardiovascular conditions should be screened for OSA with a low threshold to treat, even if OSA severity is mild. Nephroblastoma overexpressed (NOV/CCN3) protein has been identified in multiple chronic inflammatory states, most notably in obesity and more recently in OSA, even in the absence of obesity. As such, NOV may represent an important biomarker for oxidative stress in OSA and may lead to a deeper understanding of the relationship between OSA and its clinical sequelae.

FIGURE 1.

(Scheme) Diagram shows a possible mechanism for how hypoxic episodes in OSA drive inflammation and the cascade of events that increase NOV, the dysfunction of mitochondria and decreased Cardiac bioenergetics. Insulin resistance increases leading to a reduction in AKT (Protein kinase B) and AMPK. The decrease in the antioxidant HO-1 decreases the activity of PGC1α, severely decreasing mitochondrial function. Decreased AKT also drives a reduction in autophagy and may decrease mitophagy as well. The mitochondrial dysfunction is represented by the reduction in UCP1, MFN1,2 and an increase in FIS1. FIS1, indicates fission 1 protein; HO-1, heme oxygenase 1; MFN1,2, mitofusion proteins 1 and 2; NOV, nephroblastoma overexpressed; OSA, obstructive sleep apnea UCP1, uncoupling protein 1.