Temporal changes in myocardial collagen, matrix metalloproteinases, and their tissue inhibitors in the left ventricular myocardium in experimental chronic mitral regurgitation in rodents

American Journal of Physiology. Heart and Circulatory Physiology
Daniella CorporanMuralidhar Padala

Abstract

Mitral regurgitation (MR) imposes left ventricular volume overload, triggering rapid ventricular dilatation, increased myocardial compliance, and, ultimately, cardiac dysfunction. Breakdown of the extracellular matrix has been hypothesized to drive these rapid changes, partially from an imbalance in the matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)]. In the present study, we developed a rat model of severe MR that mimics the human condition and investigated the temporal changes in extracellular matrix-related genes, collagen biosynthesis proteins, and proteolytic enzymes over a 20-wk period. Male Sprague-Dawley rats were anesthetized to a surgical plane with mechanical ventilation, and a thoracotomy was performed to expose the apex. Using transesophageal ultrasound guidance, a needle was inserted into the beating heart to perforate the anterior mitral leaflet and create severe MR. Animals were survived for 20 wk, with some animals terminated at 2, 10, and 20 wk for analysis of left ventricular tissue. A sham group that underwent the same surgery without mitral leaflet perforation and MR were used as controls. At 2 wk post-MR, increased collagen gene expression was m...Continue Reading

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Citations

Sep 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Maria BloksgaardLuis A Martinez-Lemus
Jun 21, 2019·Circulation Research·Nikolaos G Frangogiannis
Dec 6, 2020·The Journal of Thoracic and Cardiovascular Surgery·Daniella CorporanMuralidhar Padala

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Methods Mentioned

BETA
imaging techniques
Profiler
PCR
Protein Assay
gene array

Software Mentioned

Prism GraphPad
Image Laboratory
GE EchoPAC

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