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Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis.
Circulation. 2013 Jun 25; 127(25):2523-34.Circ

Abstract

BACKGROUND

Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H2S) in the cardiovascular system. The deficiency of CSE in mice leads to a decreased endogenous H2S level, an age-dependent increase in blood pressure, and impaired endothelium-dependent vasorelaxation. To date, there is no direct evidence for a causative role of altered metabolism of endogenous H2S in atherosclerosis development.

METHODS AND RESULTS

Six-week-old CSE gene knockout and wild-type mice were fed with either a control chow or atherogenic paigen-type diet for 12 weeks. Plasma lipid profile and homocysteine levels, blood pressure, oxidative stress, atherosclerotic lesion size in the aortic roots, cell proliferation, and adhesion molecule expression were then analyzed. CSE-knockout mice fed with atherogenic diet developed early fatty streak lesions in the aortic root, elevated plasma levels of cholesterol and low-density lipoprotein cholesterol, hyperhomocysteinemia, increased lesional oxidative stress and adhesion molecule expression, and enhanced aortic intimal proliferation. Treatment of CSE-knockout mice with NaHS, but not N-acetylcysteine or ezetimibe, inhibited the accelerated atherosclerosis development. Double knockout of CSE and apolipoprotein E gene expression in mice exacerbated atherosclerosis development more than that in the mice with only apolipoprotein E or CSE knockout.

CONCLUSIONS

Endogenously synthesized H2S protects vascular tissues from atherogenic damage by reducing vessel intimal proliferation and inhibiting adhesion molecule expression. Decreased endogenous H2S production predisposes the animals to vascular remodeling and early development of atherosclerosis. The CSE/H2S pathway is an important therapeutic target for protection against atherosclerosis.

Authors+Show Affiliations

Department of Biology, Lakehead University, Thunder Bay, ON, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23704252

Citation

Mani, Sarathi, et al. "Decreased Endogenous Production of Hydrogen Sulfide Accelerates Atherosclerosis." Circulation, vol. 127, no. 25, 2013, pp. 2523-34.
Mani S, Li H, Untereiner A, et al. Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. Circulation. 2013;127(25):2523-34.
Mani, S., Li, H., Untereiner, A., Wu, L., Yang, G., Austin, R. C., Dickhout, J. G., Lhoták, Š., Meng, Q. H., & Wang, R. (2013). Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. Circulation, 127(25), 2523-34. https://doi.org/10.1161/CIRCULATIONAHA.113.002208
Mani S, et al. Decreased Endogenous Production of Hydrogen Sulfide Accelerates Atherosclerosis. Circulation. 2013 Jun 25;127(25):2523-34. PubMed PMID: 23704252.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. AU - Mani,Sarathi, AU - Li,Hongzhu, AU - Untereiner,Ashley, AU - Wu,Lingyun, AU - Yang,Guangdong, AU - Austin,Richard C, AU - Dickhout,Jeffrey G, AU - Lhoták,Šárka, AU - Meng,Qing H, AU - Wang,Rui, Y1 - 2013/05/23/ PY - 2013/5/25/entrez PY - 2013/5/25/pubmed PY - 2013/9/26/medline KW - apolipoprotein E KW - atherosclerosis KW - cystathionine γ-lyase KW - hydrogen sulfide KW - oxidative stress SP - 2523 EP - 34 JF - Circulation JO - Circulation VL - 127 IS - 25 N2 - BACKGROUND: Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H2S) in the cardiovascular system. The deficiency of CSE in mice leads to a decreased endogenous H2S level, an age-dependent increase in blood pressure, and impaired endothelium-dependent vasorelaxation. To date, there is no direct evidence for a causative role of altered metabolism of endogenous H2S in atherosclerosis development. METHODS AND RESULTS: Six-week-old CSE gene knockout and wild-type mice were fed with either a control chow or atherogenic paigen-type diet for 12 weeks. Plasma lipid profile and homocysteine levels, blood pressure, oxidative stress, atherosclerotic lesion size in the aortic roots, cell proliferation, and adhesion molecule expression were then analyzed. CSE-knockout mice fed with atherogenic diet developed early fatty streak lesions in the aortic root, elevated plasma levels of cholesterol and low-density lipoprotein cholesterol, hyperhomocysteinemia, increased lesional oxidative stress and adhesion molecule expression, and enhanced aortic intimal proliferation. Treatment of CSE-knockout mice with NaHS, but not N-acetylcysteine or ezetimibe, inhibited the accelerated atherosclerosis development. Double knockout of CSE and apolipoprotein E gene expression in mice exacerbated atherosclerosis development more than that in the mice with only apolipoprotein E or CSE knockout. CONCLUSIONS: Endogenously synthesized H2S protects vascular tissues from atherogenic damage by reducing vessel intimal proliferation and inhibiting adhesion molecule expression. Decreased endogenous H2S production predisposes the animals to vascular remodeling and early development of atherosclerosis. The CSE/H2S pathway is an important therapeutic target for protection against atherosclerosis. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/23704252/Decreased_endogenous_production_of_hydrogen_sulfide_accelerates_atherosclerosis_ DB - PRIME DP - Unbound Medicine ER -