Effects of adrenomedullin, C-type natriuretic peptide, and parathyroid hormone-related peptide on calcification in cultured rat vascular smooth muscle cells.
To clarify the regulating mechanism of vascular calcification, the investigators observed the effects of three vasoactive peptides, adrenomedullin (ADM), C-type natriuretic peptide (CNP), and parathyroid hormone-related peptide (PTHrP) on calcification in rat vascular smooth muscle cells (VSMCs). Beta-glycerophosphate stimulated growth and calcification in VSMCs. Adrenomedullin and CNP lowered beta-glycerophosphate-induced increase in VSMC growth. All three vasoactive peptides attenuated the increases of 45Ca accumulation, calcium content, and alkaline phosphatase activity in calcified VSMCs. As for comparing the inhibitory effects, the strongest was PTHrP. Both ADM and PTHrP increased cyclic adenosine monophosphate (cAMP) content in calcified VSMCs, but CNP upregulated cyclic guanosine monophosphate (cGMP) content. The PKA inhibitor PKAI completely reversed the inhibition of ADM on cell growth and all inhibitory effects of PTHrP on the parameters of calcification. The PKG inhibitor H8, however, strongly antagonized all the inhibitory effects of CNP on calcification. These data suggested that beta-glycerophosphate-induced calcification in VSMCs was inhibited by ADM, CNP, and PTHrP. Adrenomedullin and PTHrP inhibited VSMC calcification partially through the cAMP/PKA pathway, whereas CNP inhibited VSMC calcification through the cGMP/PKG pathway. This study could be of help in understanding the pathogenesis of vascular calcification, and providing new target for clinical treatment of cardiovascular diseases associated with vascular calcification.
Huang
Zhiyu
Z
Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, PR China.
Li
Juxiang
J
Jiang
Zhisheng
Z
Qi
Yongfen
Y
Tang
Chaoshu
C
Du
Junbao
J
D053607:Adrenomedullin; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002114:Calcinosis / Q000209:etiology*; D002118:Calcium / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005994:Glycerophosphates / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003470:Culture Media; D005994:Glycerophosphates; D044162:Parathyroid Hormone-Related Protein; D010455:Peptides; D020098:Natriuretic Peptide, C-Type; D053607:Adrenomedullin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D006152:Cyclic GMP; D002118:Calcium; C031463:beta-glycerophosphoric acid