P2 Cystathionine gamma-lyase is expressed in human atherosclerotic plaque microvessels: A possible role for hydrogen sulfide in plaque vulnerability

• DOI: 10.1016/j.niox.2014.03.052
• Publication Date: 2014-05-16T01:18:31Z
• Authors: Joost C. van den ...; Rik Mencke; Clark J. Zeebregts; Harry van Goor; Jan-Luuk Hillebrands
• Keywords: Microvessel; Vulnerable plaque; Immunostaining; Fibrous cap

Introduction Atherosclerotic plaque vulnerability is associated with intraplaque angiogenesis ( i . e . increased microvessel density). Vulnerable plaques are prone to rupture with severe risk of infarction. Hydrogen sulfide (H 2 S) is a gasotransmitter with angiogenic properties and is endogenously produced by endothelial cystathionine gamma-lyase (CSE). We hypothesize that endogenous intraplaque H 2 S production promotes angiogenesis. We here studied CSE expression in human carotid endarterectomy plaques and the effects of CSE inhibition on microvessel angiogenesis in vitro. Methods Plaques ( n = 6) and microvascular endothelial cells (HMEC-1) were studied for CSE expression using immunostaining and PCR analysis. HMEC-1 tube formation assays were performed in the presence of the selective irreversible CSE inhibitor DL-propargylglycine (PAG). Results CSE mRNA expression was abundantly expressed in atherosclerotic plaques. At the protein level, CSE co-localized with vWF-positive microvessel endothelial cells. In vitro , HMEC-1 expressed both CSE and vWF protein. CSE inhibition using PAG dose-dependently reduced tube-formation up to 24% with 10 mM PAG ( p Conclusion and discussion High levels of CSE in atherosclerotic plaques may be a potential risk for plaque vulnerability through intraplaque angiogenesis. On the other hand, CSE and H 2 S may also have protective effects in atherosclerosis, through protection against inflammation and scavenging of reactive oxygen species.