A cardioprotective insight of the cystathionine γ-lyase/hydrogen sulfide pathway

Traditionally, hydrogen sulfide (H₂S) was simply considered as a toxic and foul smelling gas, but recently H₂S been brought into the spot light of cardiovascular research and development. Since the 1990s, H₂S has been mounting evidence of physiological properties such as immune modification, vascular relaxation, attenuation of oxidative stress, inflammatory mitigation, and angiogenesis. H₂S has since been recognized as the third physiological gaseous signaling molecule, along with CO and NO [65,66]. H₂S 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 H₂S-producing enzyme in the cardiovascular system. The cystathionine γ-lyase (CSE)/H₂S 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/H₂S pathway's anti-hypertensive properties are demonstrated via aortic vasodilation through several mechanisms, including the direct stimulation of K_ATP channels of vascular smooth muscle cells (VSMCs), induction of MAPK pathway, and reduction of homocysteine buildup. Also, CSE/H₂S 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/H₂S pathway has shown a clear cardioprotective effect by preserving mitochondria function, increasing antioxidant production, and decreasing infarction injury size. However, CSE/H₂S 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 H₂S used in specific experiment models.