Isoquercitrin protects against pulmonary hypertension via inhibiting PASMCs proliferation

Summary Pulmonary vascular remodelling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension ( PAH ), and pulmonary arterial smooth muscle cells ( PASMC s) proliferation impact the long‐term prognosis of the patient. Isoquercitrin ( IQC ) is a flavonoid with anti‐oxidative, anti‐inflammatory and anti‐proliferative activations. This study aimed to investigate whether IQC could prevent PASMC s proliferation and vascular remodelling in monocrotaline ( MCT ) induced PAH . Male Wistar rats were administered with Vehicle or 0.1% IQC maintain feed after MCT (40 mg/kg) injection. Haemodynamic changes, right ventricular hypertrophy and lung morphological features were assessed 3 weeks later. MCT ‐induced PAH , pulmonary vascular remodelling and PASMC s proliferation in Vehicle‐treated rats. IQC reduced the right ventricle systolic pressure ( RVSP ), the ratio of RV / LV +S and the RV hypertrophy. IQC significantly alleviated the expression of proliferating cell nuclear antigen ( PCNA ), smooth muscle α‐actin (α‐ SMA ), and the percentage of fully muscularized small arterioles. In vitro studies, PASMC s were pretreated with IQC and stimulated with platelet‐derived growth factor ( PDGF )‐ BB (20 ng/ mL ). IQC suppressed PDGF ‐ BB ‐induced PASMC s proliferation and caused G0/G1 phase cell cycle arrest. IQC downregulated the expression of Cyclin D1 and CDK 4 as well as inhibited p27Kip1 degradation. Meanwhile, IQC negatively modulated PDGF ‐ BB ‐induced phosphorylation of PDGF ‐Rβ, Akt/ GSK 3β and ERK 1/2. IQC ameliorated MCT ‐induced pulmonary vascular remodelling via suppressing PASMC s proliferation and blocking PDGF ‐Rβ signalling pathway.