Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Krebber, Merle M; van Dijk, Christian G M; Vernooij, Robin W M; Brandt, Maarten M; Emter, Craig A; Rau, Christoph D; Fledderus, Joost O; Duncker, Dirk J; Verhaar, Marianne C; Cheng, Caroline; Joles, Jaap A
(2020) International journal of molecular sciences, volume 21, issue 18, pp. 1 - 22
(Article)
Abstract
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are pivotal regulators of extracellular matrix (ECM) composition and could, due to their dynamic activity, function as prognostic tools for fibrosis and cardiac function in left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). We conducted a
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systematic review on experimental animal models of LVDD and HFpEF published in MEDLINE or Embase. Twenty-three studies were included with a total of 36 comparisons that reported established LVDD, quantification of cardiac fibrosis and cardiac MMP or TIMP expression or activity. LVDD/HFpEF models were divided based on underlying pathology: hemodynamic overload (17 comparisons), metabolic alteration (16 comparisons) or ageing (3 comparisons). Meta-analysis showed that echocardiographic parameters were not consistently altered in LVDD/HFpEF with invasive hemodynamic measurements better representing LVDD. Increased myocardial fibrotic area indicated comparable characteristics between hemodynamic and metabolic models. Regarding MMPs and TIMPs; MMP2 and MMP9 activity and protein and TIMP1 protein levels were mainly enhanced in hemodynamic models. In most cases only mRNA was assessed and there were no correlations between cardiac tissue and plasma levels. Female gender, a known risk factor for LVDD and HFpEF, was underrepresented. Novel studies should detail relevant model characteristics and focus on MMP and TIMP protein expression and activity to identify predictive circulating markers in cardiac ECM remodeling.
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Keywords: Animal models, Extracellular matrix, Fibrosis, Heart failure with preserved ejection fraction, Left ventricular diastolic dysfunction, Matrix metalloproteinase, Systematic review, Tissue inhibitor of metalloproteinase, Molecular Biology, Spectroscopy, Catalysis, Inorganic Chemistry, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Review, Journal Article
ISSN: 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: This research was funded by Netherlands Foundation for Cardiovascular Excellence (to C.C.), Netherlands Organization for Scientific Research Vidi grant [91.714.302, to CC], the Regenerative Medicine Fellowship grant of the University Medical Center Utrecht (to C.C.), the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation [CVON2014-11 RECONNECT to C.C., J.A.J., R.W.M.V. and M.C.V.], the RECONNECT young talent grant [CVON2014-11 RECONNECT to C.G.M.v.D.], Netherlands Organization for Scientific Research Gravitation program ?Materials Driven Regeneration? [now, 024.003.013, to C.C. and M.C.V.], the MDR young talent incentives program (2020 to M.M.K.), the ?Utrecht-Eindhoven alliance? initiative, University of Missouri Research Board Grant (to C.A.E.); NIH R01 HL112998 (to C.A.E.); NIH K01 HL125503, American Heart Association Award Postdoctoral Fellowship 16POST27760052, NIH K99 HL138301 (to C.D.R.); NIH R01 HL122737, NIH R01 HL123295, and NIH HL129639. Funding Information: Funding: This research was funded by Netherlands Foundation for Cardiovascular Excellence (to C.C.), Netherlands Organization for Scientific Research Vidi grant [91.714.302, to CC], the Regenerative Medicine Fellowship grant of the University Medical Center Utrecht (to C.C.), the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation [CVON2014-11 RECONNECT to C.C., J.A.J., R.W.M.V. and M.C.V.], the RECONNECT young talent grant [CVON2014-11 RECONNECT to C.G.M.v.D.], Netherlands Organization for Scientific Research Gravitation program “Materials Driven Regeneration” [now, 024.003.013, to C.C. and M.C.V.], the MDR young talent incentives program (2020 to M.M.K.), the “Utrecht-Eindhoven alliance” initiative, University of Missouri Research Board Grant (to C.A.E.); NIH R01 HL112998 (to C.A.E.); NIH K01 HL125503, American Heart Association Award Postdoctoral Fellowship 16POST27760052, NIH K99 HL138301 (to C.D.R.); NIH R01 HL122737, NIH R01 HL123295, and NIH HL129639. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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