Echinacoside Improves Pulmonary Vascular Remodeling by Regulating the L‐ and T‐Type Ca 2+ Channels in the Prevention and Treatment of Pulmonary Hypertension

The typical pathology of pulmonary hypertension (PH) is characterized by pulmonary vasoconstriction and irreversible pulmonary vascular remodeling. Vascular remodeling is the process of structural changes and cellular rearrangement of blood vessels due to injury and is a significant factor in conditions such as PH. Echinacoside (ECH) is a phenylethanol glycoside from Tibetan herbs, and our previous study found that ECH modulated calcium channels on pulmonary artery smooth muscle cells (PASMCs) and improved pulmonary vasoconstriction. To investigate the role of ECH in improving pulmonary vascular remodeling in PH, we constructed hypoxia-induced hypoxic pulmonary hypertension (HPH) and MCT-induced pulmonary arterial hypertension (PAH) models. Transcriptomic analysis revealed significant enrichment of Cav1.2, Cav3.2, and PKC/MAPK signaling pathways in PAH rats. ECH effectively inhibited Cav1.2 and Cav3.2 protein and mRNA expression, as well as the phosphorylation levels of PKC/MAPK, in HPH and PAH. In addition, ECH effectively reduced mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) and improved pulmonary vascular remodeling in HPH and PAH rats. In short, we found that ECH improved pulmonary vascular remodeling by modulating Cav1.2 and Cav3.2/PKC/MAPK pathways. Furthermore, this improvement was effective in both HPH and PAH.