Bortezomib Alleviates Experimental Pulmonary Arterial Hypertension

摘要: Vascular remodeling and endothelial dysfunction are important pathogenic features of pulmonary arterial hypertension (PAH). There is a growing body evidence that proteasome inhibitors may be beneficial in vascular diseases by inhibiting proliferation smooth muscle cells (VSMCs) ameliorating dysfunction. Here, we evaluated whether bortezomib (BTZ) could alleviate hypoxia- monocrotaline (MCT)-induced PAH. BTZ (at doses from 1 to 100 μg/kg, or dose μg/kg) was administered mice every other day for the last 2 weeks 5-week hypoxia (10% O2) period, rats once daily Day 22 34 after MCT challenge, respectively. treatment substantially suppressed elevation right ventricular (RV) systolic pressure, RV hypertrophy, hypoxia-exposed mice. Similarly, inhibited hypertrophy MCT-injected rats. Strikingly, rescued 70% up 60, along with ...