Procyanidin B2 attenuates pathological cardiac fibrosis and inflammation: role of PPARγ.

IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Chun Xia Li, Ruo Man Wu, Qian Lin Xie, Fei Wang, Xiao Le Xu
{"title":"Procyanidin B2 attenuates pathological cardiac fibrosis and inflammation: role of PPARγ.","authors":"Chun Xia Li, Ruo Man Wu, Qian Lin Xie, Fei Wang, Xiao Le Xu","doi":"10.1097/FJC.0000000000001684","DOIUrl":null,"url":null,"abstract":"<p><p>Procyanidin B2 (PB2) is a prominent procyanidin isomer. Its effects and mechanisms in cardiac remodeling are not fully understood. Peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in regulating cardiac hypertrophy, fibrosis, and inflammation. This study aims to investigate the effect of PB2 on pathological cardiac fibrosis and inflammation, focusing on the underlying mechanisms involving PPAR-γ. In vitro, cardiac fibrosis was induced in cardiac fibroblasts using angiotensin II. In vivo, a mouse model of pathological cardiac fibrosis was generated through transverse aortic constriction to induce pressure overload. We found that PB2 inhibited proliferation, differentiation, collagen accumulation, and the NF-κB inflammation pathway in cardiac fibroblasts triggered by angiotensin II. These inhibitory effects were negated by the PPAR-γ antagonist GW9662 and RNA interference. Additionally, PB2 directly elevated PPAR-γ expression in cardiac fibroblasts. Similarly, PB2 alleviated transverse aortic constriction-induced cardiac dysfunction, myocardial fibrosis, and inflammation in mice. These cardioprotective effects of PB2 in vivo were counteracted by co-administration with GW9662. Correspondingly, the upregulation of PPAR-γ protein expression by PB2 in pressure-overloaded hearts was also counteracted by GW9662 co-administration. In conclusion, this study demonstrates that PB2 exerts protective effects against pathological cardiac fibrosis and inflammation through a PPAR-γ dependent mechanism.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cardiovascular Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FJC.0000000000001684","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0

Abstract

Procyanidin B2 (PB2) is a prominent procyanidin isomer. Its effects and mechanisms in cardiac remodeling are not fully understood. Peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in regulating cardiac hypertrophy, fibrosis, and inflammation. This study aims to investigate the effect of PB2 on pathological cardiac fibrosis and inflammation, focusing on the underlying mechanisms involving PPAR-γ. In vitro, cardiac fibrosis was induced in cardiac fibroblasts using angiotensin II. In vivo, a mouse model of pathological cardiac fibrosis was generated through transverse aortic constriction to induce pressure overload. We found that PB2 inhibited proliferation, differentiation, collagen accumulation, and the NF-κB inflammation pathway in cardiac fibroblasts triggered by angiotensin II. These inhibitory effects were negated by the PPAR-γ antagonist GW9662 and RNA interference. Additionally, PB2 directly elevated PPAR-γ expression in cardiac fibroblasts. Similarly, PB2 alleviated transverse aortic constriction-induced cardiac dysfunction, myocardial fibrosis, and inflammation in mice. These cardioprotective effects of PB2 in vivo were counteracted by co-administration with GW9662. Correspondingly, the upregulation of PPAR-γ protein expression by PB2 in pressure-overloaded hearts was also counteracted by GW9662 co-administration. In conclusion, this study demonstrates that PB2 exerts protective effects against pathological cardiac fibrosis and inflammation through a PPAR-γ dependent mechanism.

原花青素B2减轻病理性心肌纤维化和炎症:PPARγ的作用。
原花青素B2 (PB2)是一种重要的原花青素异构体。其在心脏重构中的作用和机制尚不完全清楚。过氧化物酶体增殖物激活受体γ (PPAR-γ)在调节心脏肥大、纤维化和炎症中起着至关重要的作用。本研究旨在探讨PB2对病理性心脏纤维化和炎症的影响,重点关注PPAR-γ的潜在机制。体外,血管紧张素II诱导心肌成纤维细胞纤维化。在体内,通过主动脉横缩引起压力过载,形成病理性心脏纤维化小鼠模型。我们发现PB2抑制血管紧张素II引发的心脏成纤维细胞的增殖、分化、胶原积累和NF-κB炎症通路。这些抑制作用被PPAR-γ拮抗剂GW9662和RNA干扰所抵消。此外,PB2直接升高PPAR-γ在心脏成纤维细胞中的表达。同样,PB2可减轻小鼠横主动脉缩窄引起的心功能障碍、心肌纤维化和炎症。PB2在体内的这些心脏保护作用被与GW9662共同给药所抵消。相应地,PB2对压力过载心脏中PPAR-γ蛋白表达的上调也被GW9662联合给药抵消。总之,本研究表明,PB2通过PPAR-γ依赖机制对病理性心脏纤维化和炎症具有保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
5.10
自引率
3.30%
发文量
367
审稿时长
1 months
期刊介绍: Journal of Cardiovascular Pharmacology is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. The Journal encourages submission in all aspects of cardiovascular pharmacology/medicine including, but not limited to: stroke, kidney disease, lipid disorders, diabetes, systemic and pulmonary hypertension, cancer angiogenesis, neural and hormonal control of the circulation, sepsis, neurodegenerative diseases with a vascular component, cardiac and vascular remodeling, heart failure, angina, anticoagulants/antiplatelet agents, drugs/agents that affect vascular smooth muscle, and arrhythmias. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, application of drugs to gain novel insights into physiology or pathological conditions, clinical results with new and established agents, and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases. Please note that JCVP does not publish work based on biological extracts of mixed and uncertain chemical composition or unknown concentration.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信