Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors

Abstract

Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition that is associated with oxidative stress, inflammation, and fibrosis, leading to endothelial dysfunction, arterial stiffness, and vascular insulin resistance, resulting in increased cardiovascular disease and overall mortality rates. To date, OSA remains vastly underdiagnosed and undertreated, with conventional treatments yielding relatively discouraging results for improving cardiovascular outcomes in OSA patients. As such, a better mechanistic understanding of OSA-associated cardiovascular disease (CVD) and the development of novel adjuvant therapeutic targets are critically needed. It is well-established that inappropriate mineralocorticoid receptor (MR) activation in cardiovascular tissues plays a causal role in a multitude of CVD states. Clinical studies and experimental models of OSA lead to increased secretion of the MR ligand aldosterone and excessive MR activation. Furthermore, MR activation has been associated with worsened OSA prognosis. Despite these documented relationships, there have been no studies exploring the causal involvement of MR signaling in OSA-associated CVD. Further, scarce clinical studies have exclusively assessed the beneficial role of MR antagonists for the treatment of systemic hypertension commonly associated with OSA. Here, we provide a comprehensive overview of overlapping mechanistic pathways recruited in the context of MR activation- and OSA-induced CVD and propose MR-targeted therapy as a potential avenue to abrogate the deleterious cardiovascular consequences of OSA.