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Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

Authors Vacek TP, Rehman S, Neamtu D, Yu S, Givimani S, Tyagi SC

Received 26 May 2014

Accepted for publication 20 August 2014

Published 27 February 2015 Volume 2015:11 Pages 173—183

DOI https://doi.org/10.2147/VHRM.S68415

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Daniel Duprez

Thomas P Vacek, Shahnaz Rehman, Diana Neamtu, Shipeng Yu, Srikanth Givimani, Suresh C Tyagi

Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA


Abstract: Atherosclerosis is an inflammatory process that involves activation of matrix metalloproteinases (MMPs); MMPs degrade collagen and allow for smooth-muscle cell migration within a vessel. Moreover, this begets an accumulation of other cellular material, resulting in occlusion of the vessel and ischemic events to tissues in need of nutrients. Homocysteine has been shown to activate MMPs via an increase in oxidative stress and acting as a signaling molecule on receptors like the peroxisome proliferator activated receptor- and N-methyl-d-aspartate receptor. Nitric oxide has been shown to be beneficial in some cases of deactivating MMPs. However, in other cases, it has been shown to be harmful. Further studies are warranted on the scenarios that are beneficial versus destructive. Hydrogen sulfide (H2S) has been shown to decrease MMP activities in all cases in the literature by acting as an antioxidant and vasodilator. Various MMP-knockout and gene-silencing models have been used to determine the function of the many different MMPs. This has allowed us to discern the role that each MMP has in promoting or alleviating pathological conditions. Furthermore, there has been some study into the MMP polymorphisms that exist in the population. The purpose of this review is to examine the role of MMPs and their polymorphisms on the development of atherosclerosis, with emphasis placed on pathways that involve nitric oxide, hydrogen sulfide, and homocysteine.

Keywords: homocysteine, matrix metalloproteinases, oxidative stress, bone remodeling, collagen cross-linking, hydrogen sulfide, nitric oxide

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