A cardioprotective insight of the cystathionine γ-lyase/hydrogen sulfide pathway. (1st June 2015)

• Record Type: Journal Article
• Authors: Huang, Steve; Li, Hua; Ge, Junbo
• Is Part Of: IJC heart & vasculature. Volume 7(2015)
• Page Start: 51
• Page End: 57
• Publication Date: 2015-06-01
• Subjects: Akt protein kinase B -- BCA brachiocephalic artery -- CAM chorioallantoic membrane -- CAT cysteine aminotransferase -- CBS cystathionine β-lyase -- CLP cecal ligation and puncture -- CSE cystathionine γ-lyase -- CSE KO CSE knock out -- CTO chronic total occlusion -- CX3CL1 chemokine (C-X3-C Motif) ligand 1 -- CX3CR1 CX3C chemokine receptor 1 -- EC endothelial cell -- ERK extracellular signal-regulated kinase -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- GSH-Px glutathione peroxidase -- GYY4137 morpholin-4-Ium-4-methoxyphenyl(morpholino) phosphinodithioate -- H2S hydrogen sulfide -- HUVECs human umbilical vein endothelial cells -- ICAM-1 inter cellular adhesion molecule-1 -- IMT intima–media complex thickness -- LPS lipopolysaccharide -- l-NAME NG-nitro-l-arginine methyl ester -- MAPK mitogen-activated protein kinase -- MPO myeloperoxidase -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- Nrf2 nuclear factor erythroid 2-related factor 2 -- oxLDL oxidized low density lipoprotein -- PAG DL-propagylglycine -- PPAR-γ peroxisome proliferator-activated receptor -- PTPN1 protein tyrosine phosphatase, non-receptor type 1 -- ROS reactive oxygen species -- SAH S-adenosylhomocysteine -- SAM S-adenosylmethionine -- SMCs smooth muscle cells -- SOD superoxide dismutase -- S-diclofenac 2-[(2, 6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1, 2-dithiole-3-thione-5-Yl)-phenyl ester -- VEGF vascular endothelial growth factor -- VSMCs vascular smooth muscle cells -- MST 3-mercaptopyruvate sulfurtransferase; Cystathionine γ-lyase -- Hydrogen sulfide -- Atherosclerosis -- Vasorelaxation -- Angiogenesis -- Ischemia–reperfusion injury; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Pathophysiology -- Periodicals; 616.1005
• DOI: 10.1016/j.ijcha.2015.01.010
• Languages: English
• ISSNs: 2352-9067

Abstract

Abstract: Traditionally, hydrogen sulfide (H2 S) was simply considered as a toxic and foul smelling gas, but recently H2 S been brought into the spot light of cardiovascular research and development. Since the 1990s, H2 S has been mounting evidence of physiological properties such as immune modification, vascular relaxation, attenuation of oxidative stress, inflammatory mitigation, and angiogenesis. H2 S has since been recognized as the third physiological gaseous signaling molecule, along with CO and NO [65, 66]. H2 S is produced endogenously through several key enzymes, including cystathionine β-lyase (CBE), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST)/cysteine aminotransferase (CAT). These specific enzymes are expressed accordingly in various organ systems and CSE is the predominant H2 S-producing enzyme in the cardiovascular system. The cystathionine γ-lyase (CSE)/H2 S pathway has demonstrated various cardioprotective effects, including anti-atherosclerosis, anti-hypertension, pro-angiogenesis, and attenuation of myocardial ischemia–reperfusion injury. CSE exhibits its anti-atherosclerotic effect through 3 mechanisms, namely reduction of chemotactic factor inter cellular adhesion molecule-1 (ICAM-1) and CX3CR1, inhibition of macrophage lipid uptake, and induction of smooth muscle cell apoptosis via MAPK pathway. The CSE/H2 S pathway's anti-hypertensive properties are demonstrated via aortic vasodilation through several mechanisms, including the direct stimulation of KATP channels of vascular smooth muscle cells (VSMCs), induction of MAPK pathway, and reduction of homocysteine buildup. Also, CSE/H2 S pathway plays an important role in angiogenesis, particularly in increased endothelial cell growth and migration, and in increased vascular network length. In myocardial ischemia–reperfusion injuries, CSE/H2 S pathway has shown a clear cardioprotective effect by preserving mitochondria function, increasing antioxidant production, and decreasing infarction injury size. However, CSE/H2 S pathway's role in inflammation mitigation is still clouded, due to both pro and anti-inflammatory results presented in the literature, depending on the concentration and form of H2 S used in specific experiment models.