气候变化领域集成服务门户(CCPortal): Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism

CCPortal

DOI	10.1186/s12906-024-04490-6
	Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism
	Han, Yiwei; Li, Shadi; Zhang, Zhiying; Ning, Xin; Wu, Jiajia; Zhang, Xiaoying
发表日期	2024
EISSN	2662-7671
起始页码	24
结束页码	1
卷号	24 期号:1
英文摘要	Background Bawei Chenxiang Wan (BCW) is among the most effective and widely used therapies for coronary heart disease and angina pectoris in Tibet. However, whether it confers protection through a right-ventricle (RV) myocardial metabolic mechanism is unknown. Methods Male Sprague-Dawley rats were orally administrated with BCW, which was injected concurrently with a bolus of Sugen5416, and subjected to hypoxia exposure (SuHx; 5000 m altitude) for 4 weeks. Right ventricular hypertrophy (RVH) in high-altitude heart disease (HAHD) was assessed using Fulton's index (FI; ratio of RV to left ventricle + septum weights) and heart-weight-to-body-weight ratio (HW/BW). The effect of therapeutic administration of BCW on the RVH hemodynamics was assessed through catheterization (mean right ventricular pressure and mean pulmonary artery pressure (mRVP and mPAP, respectively)). Tissue samples were used to perform histological staining, and confirmatory analyses of mRNA and protein levels were conducted to detect alterations in the mechanisms of RVH in HAHD. The protective mechanism of BCW was further verified via cell culture. Results BCW considerably reduced SuHx-associated RVH, as indicated by macro morphology, HW/BW ratio, FI, mPAP, mRVP, hypertrophy markers, heart function, pathological structure, and myocardial enzymes. Moreover, BCW can alleviate the disorder of glucose and fatty acid metabolism through upregulation of carnitine palmitoyltransferase1 alpha, citrate synthase, and acetyl-CoA and downregulation of glucose transport-4, phosphofructokinase, and pyruvate, which resulted in the reduced levels of free fatty acid and lactic acid and increased aerobic oxidation. This process may be mediated via the regulation of sirtuin 3 (SIRT3)-hypoxia-inducible factor 1 alpha (HIF1 alpha)-pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase (PDH) signaling pathway. Subsequently, the inhibition of SIRT3 expression by 3-TYP (a selective inhibitor of SIRT3) can reverse substantially the anti-RVH effect of BCW in HAHD, as indicated by hypertrophy marker and serum myocardial enzyme levels. Conclusions BCW prevented SuHx-induced RVH in HAHD via the SIRT3-HIF1 alpha-PDK/PDH signaling pathway to alleviate the disturbance in fatty acid and glucose metabolism. Therefore, BCW can be used as an alternative drug for the treatment of RVH in HAHD.
英文关键词	Right ventricular hypertrophy; Bawei Chenxiang Wan; SIRT3; HIF1 alpha; PDK; PDH
语种	英语
WOS研究方向	Integrative & Complementary Medicine
WOS类目	Integrative & Complementary Medicine
WOS记录号	WOS:001224143200003
来源期刊	BMC COMPLEMENTARY MEDICINE AND THERAPIES
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/305284
作者单位	Xizang Minzu University; Xizang Minzu University
推荐引用方式 GB/T 7714	Han, Yiwei,Li, Shadi,Zhang, Zhiying,et al. Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism[J],2024,24(1).
APA	Han, Yiwei,Li, Shadi,Zhang, Zhiying,Ning, Xin,Wu, Jiajia,&Zhang, Xiaoying.(2024).Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism.BMC COMPLEMENTARY MEDICINE AND THERAPIES,24(1).
MLA	Han, Yiwei,et al."Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism".BMC COMPLEMENTARY MEDICINE AND THERAPIES 24.1(2024).