Transgenic expression of matrix metalloproteinase-9 modulates collagen deposition in a mouse model of atherosclerosis

Atherosclerosis
Vincent LemaîtreJeanine D'Armiento

Abstract

Matrix metalloproteinase-9 (MMP-9) has been proposed to be an important modulator of atherosclerotic plaque vulnerability. We generated a transgenic (tg) model expressing human proMMP-9 in macrophages, using the scavenger receptor enhancer/promoter A. This model was crossed into the double Apoe/Timp-1 knockout background. After 16 weeks of a high-fat diet, there were no significant changes in plaque size in the proximal aortas between the four groups of the study population (Apoe(-/-), Apoe(-/-)/MMP-9tg, Apoe(-/-)/Timp-1(-/-), and Apoe(-/-)/MMP-9tg/Timp-1(-/-)), and, in the Timp-1 knockout background, MMP-9 transgenic mice and control littermates had similar micro-aneurysm formation. However, lesions in Apoe(-/-)/MMP-9tg/Timp-1(-/-) mice contained significantly more collagen compared to the three other groups (P<0.005). Culture supernatants from elicited Apoe(-/-)/MMP-9tg/Timp-1(-/-) macrophages contained higher levels of active TGF-beta than the three other groups (P<0.05), suggesting that augmented collagen deposition resulted from an increase in TGF-beta activation due to transgenic MMP-9 in the Timp-1(-/-) background. This study indicates that, in human atherosclerosis, increased MMP-9 activity could up-regulate collagen de...Continue Reading

References

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Citations

Jan 29, 2011·Current Atherosclerosis Reports·Daniel F J Ketelhuth, Magnus Bäck
Feb 21, 2013·Cardiology in Review·Dimitry A ChistiakovAlexander N Orekhov
Nov 27, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Divya MehraJeanine D'Armiento
Mar 29, 2014·PLoS Neglected Tropical Diseases·Kirsten GeneugelijkWendy W J van de Sande
Aug 27, 2014·International Immunopharmacology·Su-Jie JiaMing Zhao
Nov 22, 2011·Molecular Aspects of Medicine·Diego SbardellaMassimo Coletta
Feb 1, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Andrew C Newby
Oct 22, 2020·Mediators of Inflammation·Tiewei LiJunmei Yang

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