title: Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms.
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-γ 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.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Vacek
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Rehman
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Neamtu
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Givimani
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001808:Blood Vessels / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D066253:Vascular Remodeling; D014664:Vasodilation
chemical_list: D017382:Reactive Oxygen Species; D006710:Homocysteine; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases; D006862:Hydrogen Sulfide
keywords: bone remodeling; collagen cross-linking; homocysteine; hydrogen sulfide; matrix metalloproteinases; nitric oxide; oxidative stress