Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets
Abstract
Pulmonary arterial hypertension (PAH) is a progressive disorder marked by vascular remodeling, which leads to elevated pulmonary artery pressure, right ventricular hypertrophy, and ultimately, death. Currently, there is no cure for PAH. Magnesium lithospermate B (MLB), a major active component extracted from Salvia przewalskii, is known for its therapeutic effects in treating angina and cardiovascular damage, with demonstrated anti-inflammatory, antioxidant, and anti-apoptotic properties. However, its effects on PAH remain unclear.
In this study, we evaluated the therapeutic potential of MLB in a hypobaric hypoxia-induced rat model of PAH. Our results showed that MLB significantly reduced mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RVHI). Additionally, MLB markedly attenuated pulmonary vascular remodeling. MLB also suppressed the expression of α-smooth muscle actin (α-SMA), reduced cell apoptosis, and decreased the co-expression of α-SMA and von Willebrand factor (vWF) in lung tissues—indicating that MLB may inhibit hypoxia-induced endothelial-to-mesenchymal transition (EndMT).
Furthermore, MLB treatment downregulated the expression of several key molecules involved in hypoxic and inflammatory responses, including hypoxia-inducible factor-1α (HIF-1α), nuclear factor-kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (CDK4), Cyclin D1, RhoA, Rabusertib and rho-associated protein kinases ROCK1 and ROCK2. Potential molecular targets of MLB were also identified, including CHK1, PIM1, STK6, LKHA4, PDE5A, BRAF1, PLK1, AKT1, PAK6, PAK7, and ELNE.
In summary, our findings suggest that MLB alleviates hypobaric hypoxia-induced PAH in rats by inhibiting EndMT and may offer promising potential for the prevention and treatment of PAH.