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29 July 2016 : Animal Research  

Upregulation of Transient Receptor Potential Canonical Channels Contributes to Endotoxin-Induced Pulmonary Arterial Stenosis

Gui-Lan ChenABCDEFG, Hongni JiangABCDEFG, Fangdong ZouADE

DOI: 10.12659/MSM.898111

Med Sci Monit 2016; 22:2679-2684

Abstract

BACKGROUND: Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension.

MATERIAL AND METHODS: Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting.

RESULTS: LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels.

CONCLUSIONS: LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels.

Keywords: Cells, Cultured, Calcium - metabolism, Constriction, Pathologic, Hypertension, Pulmonary - pathology, Lipopolysaccharides - pharmacology, Muscle, Smooth, Vascular - pathology, Myocytes, Smooth Muscle - pathology, Pulmonary Artery - pathology, RNA, Messenger - metabolism, Stenosis, Pulmonary Artery - pathology, Transient Receptor Potential Channels - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750