CTRP9 Mitigates the Progression of Arteriovenous Shunt-Induced Pulmonary Artery Hypertension in Rats.

Hua Guan,Yongjian Zhang,Xiaofeng Yang,Aoqi Xiang,Yongxin Li,Tao Shi,Victor Garcia

doi:10.1155/2021/4971300

Abstract

The present study is aimed at investigating the molecular mechanism of C1q/TNF-related protein 9 (CTRP9) and providing a new perspective in arteriovenous shunt-induced pulmonary arterial hypertension (PAH). PAH was established by an arteriovenous shunt placement performed in rats. Adenovirus(Ad)-CTRP9 and Ad-green fluorescent protein viral particles were injected into the rats through the tail vein. Following 12 weeks, the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured and morphological analysis was conducted to confirm the establishment of the PAH model. The systemic elevation of CTRP9 maintained pulmonary vascular homeostasis and protected the rats from dysfunctional and abnormal remodeling. CTRP9 attenuated the pulmonary vascular remodeling in the shunt group by decreasing the mPAP and RVSP, which was associated with suppressed inflammation, apoptosis, and extracellular matrix injury. In addition, CTRP9 dramatically increased the phosphorylation of AKT and p38-MAPK in the lung tissues of shunt-operated animals. These findings suggest a previously unrecognized effect of CTRP9 in pulmonary vascular homeostasis during PAH pathogenesis.

Highlights

Pulmonary arteriole remodeling occurs in patients with pulmonary arterial hypertension (PAH), and as a result, pulmonary vascular resistance gradually increases, leading to right heart failure and premature death [1]
The mRNA and protein expression levels of C1q/TNF-related protein 9 (CTRP9) were assessed in the lung tissues and the results indicated that following injection of Ad-CTRP9 in the tail veins of the rats, CTRP9 expression was significantly increased in the sham and shunt groups compared with that noted in the adenovirus-green fluorescent protein (Ad-GFP) group (Figures 1(b)–1(d))
Since increased mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) are observed in the shunt group which could indicate the PAH, the injection of CTRP9 promoted a slight decrease of these parameters

Summary

Introduction

Pulmonary arteriole remodeling occurs in patients with pulmonary arterial hypertension (PAH), and as a result, pulmonary vascular resistance gradually increases, leading to right heart failure and premature death [1]. The pathological characteristics of PAH, namely, pulmonary artery endothelial cell dysfunction, smooth muscle hyperplasia and hypertrophy, and vascular stenosis, result in pulmonary arterial blood flow reduction and pathological changes [2,3,4]. The injury caused to pulmonary artery endothelial cells by continuous high blood flow shock is one of the possible mechanisms responsible for the formation of PAH [5, 6]. Animal experiments have shown that CTRP9 exerts a protective effect on diseases of the cardiovascular system. By inhibiting the apoptosis and inflammation of cardiomyocytes, CTRP9 reduces myocardial damage via the regulation of the function of smooth muscle cells (SMCs) and the alleviation of the pathological progression of vascular remodeling [10]. It has been shown that overexpression of CTRP9 can significantly reduce the high-fat diet-induced

Methods

Results

Conclusion