• Clin. Exp. Pharmacol. Physiol. · Mar 2017

    Isoquercitrin protects against pulmonary hypertension via inhibiting PASMCs proliferation.

    • Yongtao Zhang, Yuqian Cui, Wei Deng, Hao Wang, Weidong Qin, Chengmin Huang, Chen Li, Jianning Zhang, Yuan Guo, Dawei Wu, and Haipeng Guo.
    • Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, China.
    • Clin. Exp. Pharmacol. Physiol. 2017 Mar 1; 44 (3): 362-370.

    AbstractPulmonary vascular remodelling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) 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 PASMCs 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 PASMCs 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, PASMCs were pretreated with IQC and stimulated with platelet-derived growth factor (PDGF)-BB (20 ng/mL). IQC suppressed PDGF-BB-induced PASMCs proliferation and caused G0/G1 phase cell cycle arrest. IQC downregulated the expression of Cyclin D1 and CDK4 as well as inhibited p27Kip1 degradation. Meanwhile, IQC negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, Akt/GSK3β and ERK1/2. IQC ameliorated MCT-induced pulmonary vascular remodelling via suppressing PASMCs proliferation and blocking PDGF-Rβ signalling pathway.© 2016 John Wiley & Sons Australia, Ltd.

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