Abstract
Aim:
To investigate the role of the endogenous cystathionine γ-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.
Conclusion:
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.
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Project supported by the National Natural Science Foundation of China (No 30470693, No 30400151), the Major Project of the Ministry of Education of the People's Republic of China (No 105001) and Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT) to Xian Wang.
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Wu, Sy., Pan, Cs., Geng, B. et al. Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats. Acta Pharmacol Sin 27, 299–306 (2006). https://doi.org/10.1111/j.1745-7254.2006.00283.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00283.x
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