Pathogenic Role of Store-Operated and Receptor-Operated Ca 2 + Channels in Pulmonary Arterial Hypertension

  • Fernandez R
  • Sundivakkam P
  • Smith K
  • et al.
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Pulmonary circulation is an important circulatory system in which the body brings in oxygen. Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness are the major causes for the elevated pulmonary vascular resistance (PVR) in patients with PAH. The elevated PVR causes an increase in afterload in the right ventricle, leading to right ventricular hypertrophy, right heart failure, and eventually death. Understanding the pathogenic mechanisms of PAH is important for developing more effective therapeutic approach for the disease. An increase in cytosolic free Ca 2 + concentration ( [ Ca 2 + ] cyt ) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC migration and proliferation which lead to pulmonary vascular wall thickening and remodeling. It is thus pertinent to define the pathogenic role of Ca 2 + signaling in pulmonary vasoconstriction and PASMC proliferation to develop new therapies for PAH. [ Ca 2 + ] cyt in PASMC is increased by Ca 2 + influx through Ca 2 + channels in the plasma membrane and by Ca 2 + release or mobilization from the intracellular stores, such as sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). There are two Ca 2 + entry pathways, voltage-dependent Ca 2 + influx through voltage-dependent Ca 2 + channels (VDCC) and voltage-independent Ca 2 + influx through store-operated Ca 2+ channels (SOC) and receptor-operated Ca 2 + channels (ROC). This paper will focus on the potential role of VDCC, SOC, and ROC in the development and progression of sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in PAH.




Fernandez, R. A., Sundivakkam, P., Smith, K. A., Zeifman, A. S., Drennan, A. R., & Yuan, J. X.-J. (2012). Pathogenic Role of Store-Operated and Receptor-Operated    Ca  2 +    Channels in Pulmonary Arterial Hypertension . Journal of Signal Transduction, 2012, 1–16.

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