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Policosanol attenuates Pi‐induced calcification via AMPK‐mediated INSIGs expression in rat VSMCs
Author(s) -
Kim KyeongMin,
Kim ChangHyun,
Cho KyungHyun,
Jang WonGu
Publication year - 2021
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13530
Subject(s) - ampk , vascular smooth muscle , runx2 , chemistry , calcification , amp activated protein kinase , bone morphogenetic protein 2 , protein kinase a , pi , phosphorylation , microbiology and biotechnology , medicine , endocrinology , biochemistry , gene expression , biology , gene , smooth muscle , in vitro
Policosanol is a hypocholesterolemic derived from sugar cane and corn that downregulates blood cholesterol levels. It can further lower blood pressure and reduce liver inflammation. Policosanol can also affect vascular calcification, however, its molecular mechanisms are not well understood. This study investigated the effect of policosanol on vascular calcification and its molecular mechanism. Policosanol decreased the expression of inorganic phosphate (Pi)‐induced osteogenic genes such as distal‐less homeobox 5 (Dlx5) and runt‐related transcription factor 2 (Runx2). In addition, following policosanol treatment, adenosine monophosphate‐activated protein kinase (AMPK) phosphorylation increased in a time‐dependent manner. The constitutively active form of AMPK (CA‐AMPK) dramatically suppressed Pi‐induced Dlx5 and Runx2 protein levels. Inactivation of AMPK using compound C (Com. C; AMPK inhibitor) recovered policosanol‐suppressed Alizarin Red S staining levels. Insulin‐induced genes (INSIGs) were induced by CA‐AMPK, their overexpression suppressed Pi‐induced Dlx5 and Runx2 expression. Taken together, the results demonstrate that policosanol inhibits Pi‐induced vascular calcification by regulating AMPK‐induced INSIG expression in vascular smooth muscle cells.