4.4 Review

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

Journal

JOURNAL OF CLINICAL SLEEP MEDICINE
Volume 17, Issue 3, Pages 567-591

Publisher

AMER ACAD SLEEP MEDICINE
DOI: 10.5664/jcsm.8928

Keywords

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

Funding

  1. National Institutes of Health [MD011600, NIA R44AG059279, NIAID R21AI135935, NHLBI R01HL137282, NIDA UG3DA047717, NHLBI P01HL103453, NCI P01CA229112, NIA U01AG066623, HL126140, HL138377, U01HL128954, IPA-014264-00001, UG3HL140144]
  2. American Heart Association
  3. Lumind Foundation
  4. University of Arizona Health Sciences
  5. American Academy of Sleep Medicine Foundation
  6. American Sleep Medicine Foundation [203-JF-18, ASMF-169-SR-17]
  7. University of Arizona Health Sciences Career Development Award
  8. Faculty Seed Grant Award
  9. Patient-Centered Outcomes Research Institute [PPRND-1507-31666]
  10. Philips [HRC-1504-RETROPAP-UAZ]
  11. Whoop. Inc.
  12. PCORI [PCS-1504-30430]
  13. U.S. Department of Defense [W81XWH-14-1-0570]

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This study investigates the role of MMP-9 in OSA and cardiovascular diseases, emphasizing its importance as an inflammatory mediator in these conditions.
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.

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