Original article (Basic research)

Inhibition of PKC-βⅡ activity and amelioration of high glucose-induced angiogenesis impairment of cardiac microvasculature by nicotinamide

  • YAN Mei-ling ,
  • WANG Fa-bin ,
  • CHEN Kan-kai ,
  • et al
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  • Department of Cardiology, the Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China

Online published: 2014-09-02

Supported by

Foundation of Science and Technology Commission of Shanghai Municipality, 11ZR1427200

Abstract

Objective To explore the effects of nicotinamide on the angiogenesis impairment of microvasculature caused by high glucose and the possible mechanisms. Methods Primary cardiac microvascular endothelial cells (CMECs) were divided into the normal glucose group (NG group, 5.6 mmol/L), high glucose group (HG group, 33.3 mmol/L), high glucose+nicotinamide group (HG+N group, 33.3 mmol/L+20 mmol), and high glucose+LY333531, protein kinase C-βⅡ (PKC-βⅡ)
inhibitor, group (HG+LY group, 33.3 mmol/L+20 nmol). Lumen formation, migration, and proliferation of cells were observed after being cultured for 24 h. The expressions of PKC-βⅡ, Akt, and endothelial nitric oxide synthase (eNOS) of cells were detected by the Western blotting. Results Compared to the NG group, the ability of lumen formation, migration, and proliferation of cells of the HG group was significantly lower (P<0.05), while the ability of lumen formation, migration, and proliferation of cells of the HG+N group and HG+LY group was significantly improved. The results of Western blotting showed that compared to the NG group, the phosphorylation level of PKC-βⅡ of the HG group increased and the expressions of protein kinase B (Aktser473) and eNOSser1117 decreased (P<0.05). Nicotinamide not only inhibited the phosphorylation of PKC-βⅡ caused by high glucose, but also recovered the phosphorylation of Akt and eNOS to the level of the NG group (P<0.05). Conclusion The glucose of high concentration activates PKC-βⅡ, inhibits the activity of Akt/eNOS signaling pathway, and prevents the microvascular angiogenesis. Nicotinamide can inhibit the phosphorylation of PKC-βⅡ under high glucose condition, increase the activity of Akt/eNOS signaling pathway, and ameliorate the microvascular angiogenesis impairment.

Cite this article

YAN Mei-ling , WANG Fa-bin , CHEN Kan-kai , et al . Inhibition of PKC-βⅡ activity and amelioration of high glucose-induced angiogenesis impairment of cardiac microvasculature by nicotinamide[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2014 , 34(8) : 1137 . DOI: 10.3969/j.issn.1674-8115.2014.08.006

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