Fig. 9.

Reciprocal regulation of eNOS vs H₂S in atherosclerotic plaques. eNOS-derived NO increases bioavailability of NO in stable plaques, which would be expected to occur due to eNOS upregulation and phosphorylation (due to Akt activation); concomitantly iNOS and NOX-4 are downregulated presumably due to reduced HIF-1α. Moreover CBS and CSE positively correlate with plaque vulnerability. Simvastatin administration decreases HIF-1α expression and its downstream targets, iNOS and HO-1, whereas it increases the phosphorylation and expression of eNOS. Reduced CSE expression is associated with simvastatin administration and enhanced plaque stability (Modified by [69]). Red color indicates signaling molecules that decreased, whereas green color indicates signaling molecules that are upregulated.