Chronic Hypoxia Increases Intracellular Ca²⁺ Concentration via Enhanced Ca²⁺ Entry Through Receptor-Operated Ca²⁺ Channels in Pulmonary Venous Smooth Muscle Cells

• Peng Gongyong

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

• Li Shaoxing

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

• Hong Wei

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University The Research Center of Experiment Medicine, Guangzhou Medical University

• Hu Jinxing

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine

• Jiang Yongliang

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine

• Hu Guoping

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

• Zou Yimin

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

• Zhou Yumin

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

• Xu Juan

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

• Ran Pixin

  Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University

書誌事項

タイトル別名

• Chronic Hypoxia Increases Intracellular Ca²⁺ Concentration via Enhanced Ca²⁺ Entry Through Receptor-Operated Ca²⁺ Channels in Pulmonary Venous Smooth Muscle Cells

抄録

Background:Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular remodeling. Intracellular Ca²⁺concentration ([Ca²⁺]_i) is an essential signal for myocyte proliferation. Whether chronic hypoxia (CH) affects the basal [Ca²⁺]_iand Ca²⁺entry through store- and/or receptor-operated calcium channels (SOCC, ROCC), and whether canonical transient receptor potential (TRPC) proteins are involved in CH-induced Ca²⁺influx and proliferation in pulmonary venous smooth muscle cells (PVSMCs) is examined.Methods and Results:Rats were exposed to CH. PVSMCs were isolated from distal pulmonary veins. In freshly isolated PVSMCs, CH increased the basal [Ca²⁺]_i; removal of Ca²⁺or application of SKF-96365 reversed the elevated [Ca²⁺]_i, whereas nifedipine had no effect. Receptor-operated Ca²⁺entry (ROCE) was expressed in PVSMCs. In freshly isolated PVSMCs from CH rats, ROCE was enhanced, whereas store-operated Ca²⁺entry had no alteration. Furthermore, real-time polymerase chain reaction and western blotting showed that mRNA and protein expression level of TRPC6, but neither TRPC1 nor TRPC3, in pulmonary venous smooth muscle (PV) from CH rats and PVSMCs exposed to CH was greater than in normal PV and PVSMCs. The knockdown of TRPC6 in hypoxic PVSMCs with siRNA inhibited the enhanced ROCE and attenuated CH-induced PVSMCs proliferation.Conclusions:The enhanced Ca²⁺entry through ROCC, due to upregulated TRPC6, is a novel pathogenic mechanism contributing to the increased basal [Ca²⁺]_iin PVSMCs and excessive PVSMC proliferation during the development of HPH. (Circ J 2015; 79: 2058–2068)

収録刊行物

• Circulation Journal

  Circulation Journal 79 (9), 2058-2068, 2015

  一般社団法人 日本循環器学会

キーワード

• Calcium channels
• Proliferation
• Pulmonary hypertension
• Pulmonary vein
• Smooth muscle cells

詳細情報

• CRID: 1390001205107822080
• NII論文ID: 130005095318
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-15-0067
• ISSN: 13474820
• ISSN: 13469843
• NDL書誌ID: 026690614
• PubMed: 26134456
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026690614
• Web Site: https://www.jstage.jst.go.jp/article/circj/advpub/0/advpub_CJ-15-0067/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016111232
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
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