Matrix metalloproteinase-9 as a messenger in the cross talk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review

Abstract

Study objectives: OSA is a common sleep disorder. There is a strong link between sleep-related breathing disorders and cardiovascular and cerebrovascular diseases. Matrix metalloproteinase-9 (MMP-9) is a biological marker for extracellular matrix degradation, which plays a significant role in systemic hypertension, myocardial infarction and postmyocardial infarction heart failure, and ischemic stroke. This article reviews MMP-9 as an inflammatory mediator and a potential messenger between OSA and OSA-induced comorbidities.

Methods: We reviewed the MEDLINE database (PubMed) for publications on MMP-9, OSA, and cardiovascular disease, identifying 1,592 studies and including and reviewing 50 articles for this work.

Results: There is strong evidence that MMP-9 and tissue inhibitor of metalloproteinase-1 levels are elevated in patients with OSA (mainly MMP-9), systemic hypertension, myocardial infarction, and postmyocardial infarction heart failure. Our study showed variable results that could be related to the sample size or to laboratory methodology.

Conclusions: MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1, are a common denominator in OSA, systemic hypertension, myocardial infarction, and heart failure. This characterization makes MMP-9 a target for developing novel selective inhibitors that can serve as adjuvant therapy in patients with OSA, which may ameliorate the cardiovascular and cerebrovascular mortality associated with OSA.

Keywords: OSA; hypertension; ischemic stroke; matrix metalloproteinase-9; myocardial infarction; remodeling; tissue inhibitor of metalloproteinase-1.