Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

Abstract

Aim:The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg -1 ·d -1 ) or a positive control bosentan (30 mg·kg -1 ·d -1 ) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH.

Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats

“…VR is a major pathological change associated with hypertension and is viewed as an accurate predictor of worsening vascular function [1].Sal-A attenuates vascular remodeling in a pulmonary arterial hypertension rat model [39]. Importantly, our results showed that SABP reversed VR in SHRs.…”

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

“…In previous studies we have shown that prophylactic administration of SAA slowed the progression of pulmonary vascular remodeling, and may be associated with the Smad signaling pathway 32 . More recent evidence also reveals that SAA alleviates hypertension through inhibiting oxidative stress and TGF-β signal transduction pathway 34 .…”

“…A great deal of researches indicates that polyphenols possess extensive pharmacological activities in cardiovascular system 28 - 31 , including adjunctive treatment of microcirculation protection, endothelial protection, myocardial preservation and antioxidation. Especially, salvianolic acid A (SAA) has been gaining our attention due to its broad pharmacological effects on oxidative stress and fibrotic diseases 32 - 38 , which are closely related with PAH 39 - 41 . SAA can exert antioxidant effect through many pathways.…”

Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP‐2 and the c‐Raf/MEK/ERK pathway

“…Salvianolic acid A (SAA) is one of the most bioactive components extracted from Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese herbal medicine with anti‐inflammation, antiplatelet, antihypertension, antithrombosis, antioxidation, and antirenal disease activities, as well as cardioprotective effects on myocardial infarction . Moreover, in recent years, SAA has been shown to possess other antitumor properties, including suppressive effects on tumor proliferation through targeting endothelin A receptor in DU145 cells and on the lung cancer multidrug resistance gene MDR1 through regulating microRNA expression .…”