JCK Poster 1 (II-JCKP1)
Basics/New Insights/Others

[II-JCKP1-07] T-VDCC CaV3.1 and CaV3.2 involves in pulmonary hypertension

^○Jie Shen¹, Zixu Huang², Yuanyang Wang² (1.Department of Cardiology, Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine, China, 2.Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University, China)

Pulmonary hypertension (PH) is associated with hyperreactivity to vasoconstrictor agents and remodelling of pulmonary arteries with proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Intracellular Ca²⁺ regulates many cellular processes, such as cell cycle progression, proliferation and apoptosis. Voltage-dependent Ca²⁺ channels(VDCC) can regulate intracellular Ca²⁺ levels. L-, T- and P/Q-type channels have been identified in vascular smooth muscle cells. L-VDCC inhibitors are not so efficient in the treatment of PH. T-type channels have been cloned, and systematically named CaV3.1, CaV3.2 and CaV3.3 T-type channels, respectively. T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell proliferation in leukemia cell lines. Chronic hypoxia selectively enhances T-VDCC activity in pulmonary artery. We hypothesize that T-VDCC could constitute an alternative therapeutic target in PH.
In our research, we find that the expression of CaV3.1 and CaV3.2 are up-regulated in MCT- or hypoxia-induced PAH. Inhibition of T-VDCC CaV3.1 and CaV3.2 suppresses the proliferation of PASMC during hypoxia by delaying the G1/S phase conversion, and inhibition of CaV3.1 and CaV3.2 alleviates progression of MCT-induced PAH in rats. Further research indicates that blockade of CaV3.1 and CaV3.2 may delay G1/S phase through p-ERK/CCND1 signaling pathway. These observations may provide new mechanistic insights into pulmonary hypertension.