Protein kinase A (PKA) inhibition reduces human aortic smooth muscle cell calcification stimulated by inflammatory response and inorganic phosphate

Riki Toita, Kentaro Otani, Takahito Kawano, Satoshi Fujita, Masaharu Murata, Jeong Hun Kang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims: Smooth muscle cells (SMCs) play a role in medial vascular calcification, which can be stimulated by high levels of serum phosphate and inflammatory mediators. The aim of this study was to investigate whether mitogen-activated protein kinases (MAPKs) (p38 MAPK, ERK1/2, and JNK) and protein kinase A (PKA) can participate in inorganic phosphate (Pi)- and inflammation response-stimulated SMC calcification. Main methods: We examined the change of Pi- and/or inflammation-stimulated human aortic smooth muscle cell (HASMC) calcification in the presence and absence of inhibitors or small interfering RNAs. Key findings: Ca levels were increased in HASMCs incubated with 1.5–3.9 mM Pi, but not with 0.9 mM Pi or compared with non-Pi-treated HASMCs. Furthermore, the addition of interferon-γ (IFN-γ) increased pro-inflammatory cytokines [interleukin (IL)-1α IL-6, and tumor necrosis factor-α (TNF-α)] in media containing Raw 264.7 cells. Ca levels were significantly increased in HASMCs cultured in IFN-γ-treated medium, compared with non-IFN-γ-treated medium in the presence of Pi (0.9–2.4 mM). The inhibition of p38 MAPK and PKA decreased HASMC calcification stimulated by Pi and IFN-γ-treated medium, though PKA inhibition produced a more significant reduction in calcification than p38 MAPK inhibition. Significance: These results indicate that PKA inhibition can efficiently reduce Pi- and inflammation-stimulated SMC calcification.

Original languageEnglish
Pages (from-to)466-471
Number of pages6
JournalLife Sciences
Volume209
DOIs
Publication statusPublished - Sep 15 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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