Title |
Involvement of Rho-associated protein kinase (ROCK) and bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) in high glucose-increased alkaline phosphatase expression and activity in human coronary artery smooth muscle cells
|
---|---|
Published in |
Cardiovascular Diabetology, August 2015
|
DOI | 10.1186/s12933-015-0271-7 |
Pubmed ID | |
Authors |
Yuya Terao, Seimi Satomi-Kobayashi, Ken-ichi Hirata, Yoshiyuki Rikitake |
Abstract |
Vascular calcification is an independent risk factor for cardiovascular disease. Diabetes mellitus increases the incidence of vascular calcification; however, detailed molecular mechanisms of vascular calcification in diabetes mellitus remain unknown. We recently reported that bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) regulates osteoblast-like trans-differentiation of human coronary artery smooth muscle cells (HCASMCs). We investigated the effect of a hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin), commonly used in patients with atherosclerotic diseases and diabetes mellitus, on alkaline phosphatase (ALP) mRNA expression in aortas of streptozotocin-induced diabetic mice. We also investigated the effects of the statin, Rho-associated protein kinase (ROCK) inhibitors and BMPER knockdown on ALP mRNA expression and activity in HCASMCs cultured in high glucose-containing media. Alkaline phosphatase mRNA expression was increased in aortas of streptozotocin-induced diabetic mice, and the increase was inhibited by rosuvastatin. ALP mRNA expression and activity were increased in HCASMCs cultured in high glucose-containing media, and the increases were suppressed by rosuvastatin. This suppression was reversed by the addition of mevalonate or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. High glucose-increased ALP mRNA expression and activity were suppressed by ROCK inhibitors. Moreover, BMPER mRNA expression was increased in diabetic mouse aortas and in HCASMCs cultured in high glucose-containing media, but was not inhibited by rosuvastatin or ROCK inhibitors. Knockdown of BMPER suppressed high glucose-increased ALP activity, but not ROCK activity in HCASMCs. There are at least two independent pathways in high glucose-induced ALP activation in HCASMCs: the Rho-ROCK signaling pathway and the BMPER-dependent pathway. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 25 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 3 | 12% |
Student > Postgraduate | 3 | 12% |
Student > Ph. D. Student | 3 | 12% |
Other | 2 | 8% |
Student > Bachelor | 2 | 8% |
Other | 3 | 12% |
Unknown | 9 | 36% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 6 | 24% |
Biochemistry, Genetics and Molecular Biology | 3 | 12% |
Agricultural and Biological Sciences | 2 | 8% |
Neuroscience | 2 | 8% |
Immunology and Microbiology | 1 | 4% |
Other | 2 | 8% |
Unknown | 9 | 36% |