Polyphyllin I attenuates pressure over-load induced cardiac hypertrophy via inhibition of Wnt/β-catenin signaling pathway
Polyphyllin I attenuates pressure over-load induced cardiac hypertrophy via inhibition of Wnt/β-catenin signaling pathway
复制标题
DOI：
10.1016/j.lfs.2020.117624
复制
发表时间：
2020-07-01
期刊：
影响因子：
6.1
通讯作者：
Wei, Jin
中科院分区：
文献类型：
--
作者：
Li, Qing;Jiang, Wei;Wei, Jin
目的：心肌肥厚是心血管疾病死亡的重要危险因素之一。Wnt/β-catenin信号通路的激活被认为是心肌肥厚发病的重要机制。多叶素I（Polyphyllin I，PPI）是一种中药成分，其抗肿瘤作用部分是通过阻断Wnt/β-catenin信号通路实现的。我们的目的是WA是否PPI减弱cardiac hypertrophy.Materials and Methods：成年雄性C57 BL/6 J小鼠进行压力超负荷产生的横向主动脉缩窄（TAC）或假手术（对照组）。血管紧张素-II（Ang-II）诱导体外心肌细胞肥大。在TAC手术后每天腹腔注射PPI 4周，然后通过超声心动图和组织学分析测定心脏功能。同时，PPI可减轻TAC诱导的心肌肥厚，表现为心脏质量、心肌细胞横截面积、心肌纤维化以及心肌肥厚生物标志物ANP、BNP和β-MHC的表达增加。此外，PPI还能减轻Ang-II诱导的心肌细胞肥大。PPI降低了活性β-catenin/总β-catenin的蛋白表达，降低了GSK 3 β和Wnt靶基因c-myc、c-jun、c-fos和cyclin D1的磷酸化水平，且其抗心肌肥厚的作用被Wnt 3a所削弱。意义：PPI通过抑制Wnt/β-catenin信号通路减轻心功能不全，减轻压力超负荷引起的心肌肥厚。PPI有可能成为治疗心肌肥厚的候选药物。
Aims: Cardiac hypertrophy is one of most important risk factors for cardiovascular mortality. Activation of Wnt/beta-catenin signaling pathway is acknowledged to be an important mechanism for pathogenesis of cardiac hypertrophy. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb, has shown anticancer effect partially via interruption of Wnt/beta-catenin signaling pathway. Our aim was to WA whether PPI attenuates cardiac hypertrophy.Materials and methods: Adult male C57BL/6J mice were subjected to either pressure overload generated by transverse aortic constriction (TAC) or sham surgery (control group). Angiotensin-II (Ang-II) was used to induce cardiomyocyte hypertrophy in vitro. PPI was intraperitoneally administrated daily for 4 weeks after TAC surgery and then cardiac function was determined by echocardiography and histological analysis was performed.Key findings: PPI significantly ameliorated cardiac dysfunction of mice subjected to TAC. Meanwhile, PPI attenuated TAC induced cardiac hypertrophy indicated by blunted increase in heart mass, cross section area of cardiomyocyte, cardiac fibrosis and expression of hypertrophic biomarkers ANP, BNP and beta-MHC. In addition, PPI also ameliorated Ang-II induced cardiomyocyte hypertrophy in vitro. Importantly, PPI decreased protein expression of active beta-catenin/total beta-catenin, phosphorylation of GSK3 beta and Wnt target genes c-myc, c-jun, c-fos and cyclin D1 and its anti-hypertrophic effect was blunted by supplementation of Wnt 3a.Significance: Our results suggest that PPI attenuates cardiac dysfunction and attenuate development of pressure over-load induced cardiac hypertrophic via suppressing Wnt/beta-catenin signaling pathway. PPI might be a candidate drug for treatment of cardiac hypertrophy.