Downregulation of the CD151 Protects the Cardiac Function by the Crosstalk Between the Endothelial Cells and Cardiomyocytes Via Exosomes

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Feb 13

PMID 38349935

Authors

Luying Jiang

Jingbo Liu

Zhenjia Yang

Jianyu Wang

Wenkai Ke

Kaiyue Zhang

Chunran Zhang

Houjuan Zuo

Affiliations

Soon will be listed here.

Abstract

Background: Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear.

Method And Results: In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes.

Conclusion: Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

References

Genneback N, Hellman U, Malm L, Larsson G, Ronquist G, Waldenstrom A . Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes. J Extracell Vesicles. 2013; 2. PMC: 3760655. DOI: 10.3402/jev.v2i0.20167. View

Viereck J, Bang C, Foinquinos A, Thum T . Regulatory RNAs and paracrine networks in the heart. Cardiovasc Res. 2014; 102(2):290-301. DOI: 10.1093/cvr/cvu039. View

Zuo H, Liu Z, Liu X, Yang J, Liu T, Wen S . CD151 gene delivery after myocardial infarction promotes functional neovascularization and activates FAK signaling. Mol Med. 2009; 15(9-10):307-15. PMC: 2710288. DOI: 10.2119/molmed.2009.00025. View

Takeda N, Manabe I . Cellular Interplay between Cardiomyocytes and Nonmyocytes in Cardiac Remodeling. Int J Inflam. 2011; 2011:535241. PMC: 3175723. DOI: 10.4061/2011/535241. View

Tripathi D, Biswas B, Manhas A, Singh A, Goyal D, Gaestel M . Proinflammatory Effect of Endothelial Microparticles Is Mitochondria Mediated and Modulated Through MAPKAPK2 (MAPK-Activated Protein Kinase 2) Leading to Attenuation of Cardiac Hypertrophy. Arterioscler Thromb Vasc Biol. 2019; 39(6):1100-1112. DOI: 10.1161/ATVBAHA.119.312533. View

Li H, Zhang X, Wang F, Zhou L, Yin Z, Fan J . MicroRNA-21 Lowers Blood Pressure in Spontaneous Hypertensive Rats by Upregulating Mitochondrial Translation. Circulation. 2016; 134(10):734-51. PMC: 5515592. DOI: 10.1161/CIRCULATIONAHA.116.023926. View

Salunkhe S, Dheeraj , Basak M, Chitkara D, Mittal A . Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: Strategies and significance. J Control Release. 2020; 326:599-614. DOI: 10.1016/j.jconrel.2020.07.042. View

Yang D, Liu H, Liu F, Tang N, Guo Z, Ma S . The Roles of Noncardiomyocytes in Cardiac Remodeling. Int J Biol Sci. 2020; 16(13):2414-2429. PMC: 7378633. DOI: 10.7150/ijbs.47180. View

Li S, Li X, Yang S, Pi H, Li Z, Yao P . Proteomic Landscape of Exosomes Reveals the Functional Contributions of CD151 in Triple-Negative Breast Cancer. Mol Cell Proteomics. 2021; 20:100121. PMC: 8379346. DOI: 10.1016/j.mcpro.2021.100121. View

10.

Cowan P, Tsang D, Pedic C, Abbott L, Shinkel T, dApice A . The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and contains critical Sp1 and GATA binding sites. J Biol Chem. 1998; 273(19):11737-44. DOI: 10.1074/jbc.273.19.11737. View

11.

Aday S, Hazan-Halevy I, Chamorro-Jorganes A, Anwar M, Goldsmith M, Beazley-Long N . Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo. Mol Ther. 2021; 29(7):2239-2252. PMC: 8261169. DOI: 10.1016/j.ymthe.2021.03.015. View

12.

Ritterhoff J, Tian R . Metabolism in cardiomyopathy: every substrate matters. Cardiovasc Res. 2017; 113(4):411-421. PMC: 5852620. DOI: 10.1093/cvr/cvx017. View

13.

Shi Y, Ding Y, Li G, Wang L, Osman R, Sun J . Discovery of Novel Biomarkers for Diagnosing and Predicting the Progression of Multiple Sclerosis Using TMT-Based Quantitative Proteomics. Front Immunol. 2021; 12:700031. PMC: 8417809. DOI: 10.3389/fimmu.2021.700031. View

14.

Loichot C, Jesel L, Tesse A, Tabernero A, Schoonjans K, Roul G . Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions. Am J Physiol Heart Circ Physiol. 2006; 291(1):H161-6. DOI: 10.1152/ajpheart.01065.2004. View

15.

Tanai E, Frantz S . Pathophysiology of Heart Failure. Compr Physiol. 2016; 6(1):187-214. DOI: 10.1002/cphy.c140055. View

16.

Wu Y, Lin X, Hong H, Fung Y, Cao X, Tse J . Endothelium-targeted delivery of PPARδ by adeno-associated virus serotype 1 ameliorates vascular injury induced by hindlimb ischemia in obese mice. Biomed Pharmacother. 2022; 151:113172. DOI: 10.1016/j.biopha.2022.113172. View

17.

Hogrebe A, von Stechow L, Bekker-Jensen D, Weinert B, Kelstrup C, Olsen J . Benchmarking common quantification strategies for large-scale phosphoproteomics. Nat Commun. 2018; 9(1):1045. PMC: 5849679. DOI: 10.1038/s41467-018-03309-6. View

18.

Takeda Y, Kazarov A, Butterfield C, Hopkins B, Benjamin L, Kaipainen A . Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro. Blood. 2006; 109(4):1524-32. PMC: 1794066. DOI: 10.1182/blood-2006-08-041970. View

19.

Hemler M . Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol. 2005; 6(10):801-11. DOI: 10.1038/nrm1736. View

20.

Bang C, Batkai S, Dangwal S, Gupta S, Foinquinos A, Holzmann A . Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014; 124(5):2136-46. PMC: 4001534. DOI: 10.1172/JCI70577. View