In lung tissues of MCT-PAH rats, EGF levels were elevated, and Calpain-1 and Calpain-2 were upregulated.80 Additionally, Calpain-4 was upregulated in the lungs of mice with hypoxia-PH.80 These changes resulted in increased levels of PDGF, activation of the TGF-β1/Smad2/3 pathway, excessive deposition of COL1, and thickening of the smooth muscle layer of pulmonary arterioles, contributing to pulmonary vascular remodeling and the development of PH.80 This evidence concerns the gene CAPN2 and pulmonary arterial hypertension.