{"title":"Overexpression of TRPV6 Inhibits Coronary Atherosclerosis–Related Inflammatory Response and Cell Apoptosis via the PKA/UCP2 Pathway","authors":"Lei Zheng, Huiying Zhang, Xuewen Li","doi":"10.1155/2024/7053116","DOIUrl":null,"url":null,"abstract":"<p><b>Objective:</b> This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6/PKA/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD).</p><p><b>Methods:</b> We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit-8 (CCK-8) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6/PKA/UCP2 signaling pathway and apoptosis-related factors was detected using western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><b>Results:</b> TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low-density lipoprotein (ox-LDL)–treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor-alpha (TNF-<i>α</i>), interleukin-6 (IL-6), and interleukin-1 beta (IL-1<i>β</i>). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe-TRPV6 + si-PKA group.</p><p><b>Conclusions:</b> In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/7053116","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/7053116","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
Objective: This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6/PKA/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD).
Methods: We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit-8 (CCK-8) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6/PKA/UCP2 signaling pathway and apoptosis-related factors was detected using western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR).
Results: TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low-density lipoprotein (ox-LDL)–treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe-TRPV6 + si-PKA group.
Conclusions: In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway.
期刊介绍:
Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged.
Subject areas include (but are by no means limited to):
Acute coronary syndrome
Arrhythmias
Atherosclerosis
Basic cardiac electrophysiology
Cardiac catheterization
Cardiac remodeling
Coagulation and thrombosis
Diabetic cardiovascular disease
Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF)
Hyperlipidemia
Hypertension
Ischemic heart disease
Vascular biology
Ventricular assist devices
Molecular cardio-biology
Myocardial regeneration
Lipoprotein metabolism
Radial artery access
Percutaneous coronary intervention
Transcatheter aortic and mitral valve replacement.