School of Bioscience & Bioengineering, South China University of Technology, 382 Waihuan Road East, Guangzhou Higher Education Mega Centre, Guangzhou, Guangdong Province, 510006, China.
Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, No.100 Waihuan Xi Road, Guangzhou Higher Education Mega Centre, Guangzhou, Guangdong Province, 510006, China.
Biomed Pharmacother. 2018 May;101:371-378. doi: 10.1016/j.biopha.2018.02.078. Epub 2018 Mar 22.
Right heart failure and pulmonary artery remodeling resulting from increased left heart pressure are prevalent in a clinical setting, and the specific pathological feature exhibits cancer-like cell proliferation in lung. STVNa has been previously demonstrated its anti-proliferation property. In this study, we want to verify the therapeutic effect of STVNa against right ventricle hypertrophy and pulmonary artery remodeling in rats induced by transverse aortic constriction (TAC). The results show that TAC surgery increased mean right ventricle pressure (mRVP) less in the STVNa group than that in the vehicle group (11.81 vs 22.71 mmHg/ml, p < 0.01). STVNa treatment reduced the right ventricle cardiomyocyte area (p < 0.05) and the proliferation of pathological smooth muscle cells proving by PCNA immunohistochemical staining. Gene expression of brain natriuretic peptide (BNP), smooth muscle actin (SMA) and CD31 assessed by real-time polymerase chain reaction were confirmed the above results. Also, STVNa treatment decreased the lung fibrosis content and alleviated the inflammation infiltration. The expression of ET-1 and the phosphorylation of signal-regulated kinase (ERK) were lower in STVNa group compared to vehicle group (p < 0.05). In summary, STVNa could relieve right ventricle hypertrophy and pulmonary artery remodeling formation in rats after 9 weeks of TAC surgery by reducing ET-1 expression and suppressing ERK phosphorylation signal and subsequently inhibiting cell proliferation.
右心衰竭和肺动脉重构是由左心压力升高引起的，在临床环境中很常见，其特定的病理特征表现为肺部类似癌细胞的增殖。STVNa 先前已被证明具有抗增殖特性。在这项研究中，我们想要验证 STVNa 对横主动脉缩窄（TAC）诱导的大鼠右心室肥厚和肺动脉重构的治疗效果。结果表明，TAC 手术后，STVNa 组的平均右心室压力（mRVP）比对照组降低（11.81 对 22.71 mmHg/ml，p < 0.01）。STVNa 治疗减少了右心室心肌细胞面积（p < 0.05）和增殖的病理平滑肌细胞，通过 PCNA 免疫组化染色证明。实时聚合酶链反应评估的脑钠肽（BNP）、平滑肌肌动蛋白（SMA）和 CD31 的基因表达证实了上述结果。此外，STVNa 治疗降低了肺纤维化含量并减轻了炎症浸润。与对照组相比，STVNa 组的 ET-1 表达和信号调节激酶（ERK）磷酸化降低（p < 0.05）。综上所述，STVNa 可通过降低 ET-1 表达和抑制 ERK 磷酸化信号，进而抑制细胞增殖，减轻 TAC 手术后 9 周大鼠的右心室肥厚和肺动脉重构形成。
