The antihypertension effect of hydrogen sulfide (H2S) is induced by activating VEGFR2 signaling pathway

Emerging roles of cystathionine β-synthase in various forms of cancer

“…Moreover, in co-culture experiments, Eca109 cells with CBS overexpression stimulated more angiogenesis and lymphangiogenesis than the responses induced by wild-type Eca109 cells, an effect which occurred, at least in part, via the upregulation of VEGF protein expression [ 76 ]. These findings are consistent with multiple sets of studies focusing on the pro-angiogenic role of H 2 S; it has been well established that (a) pharmacological H 2 S donators stimulate angiogenesis; (b) certain endogenous pro-angiogenic hormones, including VEGF, utilize the cellular biosynthesis of H 2 S to exert their pro-angiogenic action and (c) H 2 S can upregulate various elements of multiple angiogenic pathways, including VEGF, VEGF receptor and several other pro-angiogenic factors and mediators [ 52 , 64 , 70 , [122] , [123] , [124] , [125] , [126] , [131] , [132] , [133] , [134] , [135] , [136] , [137] , [138] , [139] ].…”

“…An additional pro-angiogenic mechanism may involve the cooperative interaction between H 2 S and eNOS-derived NO in the activation of cGMP signalling; in this system NO serves as the primary activator of this system, while H 2 S prolongs the action of cGMP by inhibiting cGMP phosphodiesterase [ 126 , 132 , 135 ]. Further mechanisms may include the upregulation of VEGF and its receptor [ 2 , 48 , 64 , 70 , 76 , [122] , [123] , [124] , [125] , [126] , [131] , [132] , [133] , [134] , [135] , [136] , [137] , [138] , [139] ] and the consequent activation of this system (possibly, in part, also via Flt induction [ 64 ]), the induction of the angiopoietin/tie system, possibly via the upregulation of Ang1 and Ang2 system [ 64 ] as well as though the upregulation of Tie [ 64 ] and, possibly, the induction of the adrenomedullin system [ 48 ] and the induction of various additional endothelial cell receptors with pro-angiogenic functions (CXCR1, VCAM1) [ 48 , 64 ]. Finally, a further mechanism may be simply related to the fact that tumors are often hypoxic, and hypoxia prolongs the biological half-life of H 2 S, which, in turn, may be more effective in exerting its various pro-angiogenic actions.…”

Exposome and foetoplacental vascular dysfunction in gestational diabetes mellitus

“…This phenomenon results in a lower activity of NHE1, reducing the H + efflux ending in intracellular acidification, which is a condition that diminishes eNOS activity in HUVECs (Fleming et al, 2004;Ramírez et al, 2018). However, H 2 S released from the spontaneous donor GYY4137 increases the eNOS expression and activity in HUVECs (Zhu et al, 2021). Thus, H 2 S may have a dual effect on eNOS activity depending on the predominant cell signalling mechanism triggered by this gasotransmitter.…”

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

“…Besides, another study reports that exogenous H 2 S improves the migration of high-glucose-treated HUVECs by suppressing the expression of DNA methyltransferase 1 protein, resulting in the subsequent elevation of miR-126-3p [ 86 ]. Moreover, recent studies indicate that treatment with GYY4137 suppresses the migration of HUVECs by increasing protein S-sulfuration [ 87 ] and activating the PI3K/AKT pathway [ 88 ]. Although the changes in the effects have been suggested to be due to the nature of the donor as compared to NaHS, which has been mostly used in the other studies, the area needs further exploration.…”