Pulmonary arterial hypertension (PAH) is classified as group 1 of pulmonary hypertension. PAH is a progressive and fatal disease of the pulmonary artery. The major pathogenesis of PAH is sustained vasoconstriction and vascular remodeling of the pulmonary artery. These pathogeneses cause progressive elevations in pulmonary vascular resistance and pulmonary arterial pressure (PAP) in PAH patients. Elevated PAP leads to right heart failure and finally death. A central aspect of pulmonary vascular remodeling is medial hypertrophy, which is caused by the enhanced proliferation and reduced apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Excitable abnormality in the pulmonary artery of PAH patients are mostly mediated by an elevated cytosolic [Ca²⁺]. Enhanced Ca²⁺ signaling have been reported in PASMCs from PAH patients. PASMCs express several Ca²⁺-permeable channels including voltage-dependent Ca²⁺ channels, receptor-operated Ca²⁺ channels, and store-operated Ca²⁺ channels. The expression levels of these Ca²⁺ channels are increased in the lung tissues and PASMCs of PAH patients. Targeting these Ca²⁺ channels in PASMCs may help develop novel therapeutic approach for PAH.

Excitation–transcription (E-T) coupling can initiate and modulate essential physiological or pathological responses in cells, such as neurons and cardiac myocytes. Although vascular myocytes also exhibit E-T coupling in response to membrane depolarization, the underlying molecular mechanisms are unknown. Our study reveals that E-T coupling in vascular myocytes converts intracellular Ca²⁺ signals into selective gene transcription related to chemotaxis, leukocyte adhesion, and inflammation. Our discovery identifies a mechanism for vascular remodeling as an adaptation to increased circumferential stretch.

Hepatic stellate cells (HSCs) play a significant role in the development of chronic liver diseases. Hepatic damage activates HSCs and results in hepatic fibrosis. The functions of activated HSCs require an increase in the cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt). However, the regulatory mechanisms underlying Ca²⁺ signaling in activated HSCs remain largely unknown. CaSRs are functionally expressed in activated HSCs and regulate Ca²⁺ signaling and cell proliferation. The present results provide insights into the molecular mechanisms underlying hepatic fibrosis and will contribute to the development of potential therapeutic targets.