Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension

Abstract

The aim of the present study was to investigate the effects of paclitaxel (PTX), at a non-cytotoxic concentration, on pulmonary vascular remodeling (PVR) in rats with pulmonary hypertension (PAH), and to explore the mechanisms underlying the PTX-mediated reversal of PVR in PAH. A total of 36 rats were divided into control group (n=12), model group (n=12) receiving a subcutaneous injection of monocrotaline (60 mg/kg) in the back on day 7 following left pneumonectomy and PTX group (n=12) with PTX (2 mg/kg) injection via the caudal vein 3 weeks following establishing the model. The degree of PVR among all groups, as well as the expression levels of Ki67, p27Kip1 and cyclin B1, were compared. The mean pulmonary artery pressure, right ventricular hypertrophy index [right ventricle/(left ventricle + septum) ratio] and the thickness of the pulmonary arterial tunica media in the model group were 58.34±2.01 mmHg, 0.64±0.046 and 65.3±3.3%, respectively, which were significantly higher when compared with 23.30±1.14 mmHg, 0.32±0.028 and 16.2±1.3% in the control group, respectively (P<0.01). The mean pulmonary artery pressure, right ventricular hypertrophy index and thickness of the pulmonary arterial tunica media in the PTX group were 42.35±1.53 mmHg, 0.44±0.029 and 40.5±2.6%, respectively, which were significantly lower when compared with the model group (P<0.01). Compared with the control group, the expression levels of Ki67 and cyclin B1 in the model group were significantly increased (P<0.01), while p27Kip1 expression was significantly reduced (P<0.01). Following PTX intervention, the expression levels of Ki67 and cyclin B1 were significantly reduced when compared with the model group (P<0.01), while p27Kip1 expression was significantly increased (P<0.01). The results of the present study suggest that PTX, administered at a non-cytotoxic concentration, may reduce PAH in rats, and prevent the effects of PVR in PAH. These effects of PTX may be associated with increased expression of p27Kip1 and decreased expression of cyclin B1.

The role of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway in the pulmonary vascular remodeling of pulmonary arterial hypertension in rats

“…The results reported by Nishimura et al [19] were consistent with the present study. Our previous studies comparing the establishment of a PAH animal model using four different methods (an abdominal aortocaval shunt, a left pneumonectomy, an MCT resection, and a left pneumonectomy with MCT injection) also confirmed the above results [17].…”

“…The mPAP was recorded as the Ref. [17]. Tissue samples from the right lung and the entire heart were taken from each rat.…”

Traditional Herbal Medicine Discovery for the Treatment and Prevention of Pulmonary Arterial Hypertension

“…Given the excessive PASMC proliferation as one of the main characteristics of PAH, researchers have applied paclitaxel to PAH, another vascular disease, and explored its action mechanisms. The results suggested that paclitaxel has positive effects on MCT-induced PAH in rats, which may be associated with the increased expression of p27 Kip1 and decreased expression of cyclin B1 ( Zhao et al, 2019 ), or suppressed FoxO1-mediated autophagy ( Feng et al, 2019b ). Moreover, paclitaxel was applied to another PAH mouse model induced by Schistosoma mansoni and obtained satisfactory effect by blocking proximate Th2 inflammation rather than suppressing distal TGF-β activation ( Kassa et al, 2019 ).…”

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo

“…[11][12][13][14][15] Paclitaxel has been recently evaluated as a remodeling agent for PAH. [16] Sotatercept has been recently been evaluated in a clinical trial with favorable results (the PULSAR study) [17]. We investigated whether the drugs paclitaxel, sotetercept and iloprost could be administered as aerosol with jet and ultrasound nebulizers.…”