Cardiac restricted overexpression of membrane type-1 matrix metalloproteinase causes adverse myocardial remodeling following myocardial infarction.

The Journal of Biological Chemistry
Francis G SpinaleAlbert J Sinusas

Abstract

The membrane type-1 matrix metalloproteinase (MT1-MMP) is a unique member of the MMP family, but induction patterns and consequences of MT1-MMP overexpression (MT1-MMPexp), in a left ventricular (LV) remodeling process such as myocardial infarction (MI), have not been explored. MT1-MMP promoter activity (murine luciferase reporter) increased 20-fold at 3 days and 50-fold at 14 days post-MI. MI was then induced in mice with cardiac restricted MT1-MMPexp (n = 58) and wild type (WT, n = 60). Post-MI survival was reduced (67% versus 46%, p < 0.05), and LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT (41 ± 2 versus 32 ± 2%,p < 0.05). In the post-MI MT1-MMPexp mice, LV myocardial MMP activity, as assessed by radiotracer uptake, and MT1-MMP-specific proteolytic activity using a specific fluorogenic assay were both increased by 2-fold. LV collagen content was increased by nearly 2-fold in the post-MI MT1-MMPexp compared with WT. Using a validated fluorogenic construct, it was discovered that MT1-MMP proteolytically processed the pro-fibrotic molecule, latency-associated transforming growth factor-1 binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by 4-fold in the po...Continue Reading

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Citations

Nov 24, 2012·American Journal of Physiology. Cell Physiology·Edie C GoldsmithFrancis G Spinale
Jun 15, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Juozas A ZavadzkasFrancis G Spinale
Oct 12, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Jennifer A DixonFrancis G Spinale
Aug 21, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Rugmani Padmanabhan IyerMerry L Lindsey
Mar 20, 2014·Molecular Pharmaceutics·Sander M J van DuijnhovenHolger Grüll
May 2, 2014·Biochemical Pharmacology·Francis G Spinale, Francisco Villarreal
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May 29, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Anis HannaNikolaos G Frangogiannis
Sep 9, 2021·Biology Open·Tania Martins-Marques

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