Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats.
OBJECTIVE
To investigate the role of the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H2S) pathway in vascular calcification in vivo.


METHODS
A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi-quantitative reverse-transcription polymerase chain reaction. The calcium content, 45Ca2+ accumulation and alkaline phosphatase (ALP) activity were measured. H2S production and CSE activity were measured.


RESULTS
von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, 45Ca2+ accumulation and ALP activity in calcified arteries increased by 6.77-, 1.42-, and 1.87-fold, respectively, compared with controls. The expression of the OPN gene was upregulated (P<0.01). Expression of the CSE gene was downregulated. However, calcium content, 45Ca2+ uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and 45Ca2+ accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5% lower in the low-dosage NaHS group than in the VDN group, respectively (P<0.01), and the calcium content and deposition of 45Ca2+ and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high-dosage NaHS group than in the VDN group, respectively (P<0.01). The expression of the OPN gene was downregulated.


CONCLUSIONS
The production of H2S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H2S can ameliorate vascular calcification, suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.
Institute of Cardiovascular Disease, Peking University First Hospital. Beijing 100034 China.
Sheng-ying
SY
Wu
Chun-shui
CS
Pan
Bin
B
Geng
Jing
J
Zhao
Fang
F
Yu
Yong-zheng
YZ
Pang
Chao-shu
CS
Tang
Yong-fen
YF
Qi
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002114:Calcinosis / Q000139:chemically induced / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002762:Cholecalciferol; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009538:Nicotine; D053495:Osteopontin; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013440:Sulfides / Q000494:pharmacology*
D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D013440:Sulfides; D053495:Osteopontin; D002762:Cholecalciferol; D009538:Nicotine; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D002118:Calcium; D006862:Hydrogen Sulfide