Key result
Paclitaxel administered at a non-cytotoxic concentration significantly reduced mean pulmonary artery pressure (42.35 vs 58.34 mmHg, P<0.01) and prevented pulmonary vascular remodeling in rats with pulmonary hypertension.
Why the study?
The effects of non-cytotoxic paclitaxel on pulmonary vascular remodeling in pulmonary hypertension and its underlying mechanisms remained to be investigated.
Does paclitaxel reduce pulmonary vascular remodeling in a rat model of pulmonary hypertension?
Does paclitaxel reduce pulmonary vascular remodeling in a rat model of pulmonary hypertension?
In a rat model of pulmonary hypertension, low-dose paclitaxel significantly reduced pulmonary artery pressure and vascular remodeling, associated with increased p27Kip1 and decreased cyclin B1 expression.
Answers are grounded in this paper and cite their sources.
Does not support clinical use of paclitaxel in pulmonary hypertension; leaves open need for human translation studies.
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.
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Zhao et al. (2018) studied Pulmonary hypertension (n=36). Paclitaxel vs. Model group (monocrotaline only) was evaluated on Mean pulmonary artery pressure (mPAP) (p=<0.01). Paclitaxel administered at a non-cytotoxic concentration significantly reduced mean pulmonary artery pressure (42.35 vs 58.34 mmHg, P<0.01) and prevented pulmonary vascular remodeling in rats with pulmonary hypertension.
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