Salusin-β contributes to vascular inflammation associated with pulmonary arterial hypertension in rats

    loading  Checking for direct PDF access through Ovid

Abstract

Objective

Inflammation is closely linked to pulmonary arterial hypertension (PAH). Salusin-β, a bioactive peptide, has been reported to participate in vascular inflammation. We therefore hypothesized that salusin-β contributes to monocrotaline (MCT)-induced PAH in rats.

Methods

Male Sprague-Dawley rats were treated with MCT (60 mg kg−1, single intraperitoneal injection). Salusin-β expression in the lungs of the MCT-treated rats was evaluated using immunofluorescence staining, western blot, and real-time PCR. For salusin-β blockade assay, rats injected with MCT were given a chronic infusion of anti-salusin-β immunoglobulin G (IgG) (salusin-β blocker, 1.0 μg kg−1 h−1) or isotype-matched control IgG. Four weeks after MCT+anti-salusin-β treatment, the effects of salusin-β blockade were determined using hemodynamics, western blot, real-time PCR, and immunohistochemical detection. The effect of salusin-β on human pulmonary arterial endothelial cell (HPAEC) function was detected by adhesion and tube formation experiments in vitro.

Results

Salusin-β expression was significantly increased in the lungs of the MCT-treated rats, and immunofluorescence results showed that salusin-β was predominantly expressed in pulmonary macrophages and vascular endothelial cells. Salusin-β blockade significantly ameliorated PAH by acting against pulmonary vascular remodeling, decreasing macrophage infiltration, and reducing pro-inflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity in the lungs of the MCT-treated rats. In addition, salusin-β could induce cell adhesion and accelerate angiogenesis by activating the NF-κB pathway and promoting pro-inflammatory cytokine expression in the cultured HPAECs. This effect was suppressed by addition of the NF-κB inhibitor, N-acetyl-L-cysteine.

Conclusions

Salusin-β plays a crucial role in the development of MCT-induced PAH models.

Related Topics

    loading  Loading Related Articles