Extracellular Vesicles in Metabolic and Vascular Insulin Resistance

Overview

Journal J Vasc Res

Specialty Cardiology & Vascular Diseases

Date 2024 Apr 14

PMID 38615667

Authors

Steven K Malin

Uta Erdbrugger

Affiliations

Soon will be listed here.

Abstract

Background: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear.

Summary: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes.

Key Message: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.

References

Brennan E, Wang B, McClelland A, Mohan M, Marai M, Beuscart O . Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis. Diabetes. 2017; 66(8):2266-2277. DOI: 10.2337/db16-1405. View

Kim H, Song K, Chung J, Lee K, Lee S . Platelet microparticles induce angiogenesis in vitro. Br J Haematol. 2004; 124(3):376-84. DOI: 10.1046/j.1365-2141.2003.04773.x. View

Horn P, Cortese-Krott M, Amabile N, Hundsdorfer C, Kroncke K, Kelm M . Circulating microparticles carry a functional endothelial nitric oxide synthase that is decreased in patients with endothelial dysfunction. J Am Heart Assoc. 2013; 2(1):e003764. PMC: 3603231. DOI: 10.1161/JAHA.112.003764. View

Diehl P, Fricke A, Sander L, Stamm J, Bassler N, Htun N . Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res. 2012; 93(4):633-44. PMC: 3291092. DOI: 10.1093/cvr/cvs007. View

Wang J, Su C, Wang Y, Huang Y, Yang Z, Chen L . Elevated circulating endothelial microparticles and brachial-ankle pulse wave velocity in well-controlled hypertensive patients. J Hum Hypertens. 2008; 23(5):307-15. DOI: 10.1038/jhh.2008.137. View

Jansen F, Yang X, Franklin B, Hoelscher M, Schmitz T, Bedorf J . High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation. Cardiovasc Res. 2013; 98(1):94-106. DOI: 10.1093/cvr/cvt013. View

Ross M, Wekesa A, Phelan J, Harrison M . Resistance exercise increases endothelial progenitor cells and angiogenic factors. Med Sci Sports Exerc. 2013; 46(1):16-23. DOI: 10.1249/MSS.0b013e3182a142da. View

Lu G, Xu R, Zhang S, Qiao Q, Shen L, Li M . Alteration of circulatory platelet microparticles and endothelial microparticles in patients with chronic kidney disease. Int J Clin Exp Med. 2015; 8(9):16704-8. PMC: 4659095. View

Ragland T, Heiston E, Ballantyne A, Stewart N, La Salvia S, Musante L . Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome. Physiol Rep. 2023; 11(1):e15530. PMC: 9810789. DOI: 10.14814/phy2.15530. View

10.

Ceriello A, Motz E . Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004; 24(5):816-23. DOI: 10.1161/01.ATV.0000122852.22604.78. View

11.

Wilhelm E, Gonzalez-Alonso J, Parris C, Rakobowchuk M . Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells. Am J Physiol Heart Circ Physiol. 2016; 311(5):H1297-H1310. DOI: 10.1152/ajpheart.00516.2016. View

12.

Wahl P, Wehmeier U, Jansen F, Kilian Y, Bloch W, Werner N . Acute Effects of Different Exercise Protocols on the Circulating Vascular microRNAs -16, -21, and -126 in Trained Subjects. Front Physiol. 2017; 7:643. PMC: 5183575. DOI: 10.3389/fphys.2016.00643. View

13.

Fruhbeis C, Helmig S, Tug S, Simon P, Kramer-Albers E . Physical exercise induces rapid release of small extracellular vesicles into the circulation. J Extracell Vesicles. 2015; 4:28239. PMC: 4491306. DOI: 10.3402/jev.v4.28239. View

14.

Tushuizen M, Diamant M, Heine R . Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes. Postgrad Med J. 2005; 81(951):1-6. PMC: 1743184. DOI: 10.1136/pgmj.2004.020511. View

15.

Amabile N, Rautou P, Tedgui A, Boulanger C . Microparticles: key protagonists in cardiovascular disorders. Semin Thromb Hemost. 2010; 36(8):907-16. DOI: 10.1055/s-0030-1267044. View

16.

Steinberg H, Chaker H, LEAMING R, Johnson A, Brechtel G, Baron A . Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996; 97(11):2601-10. PMC: 507347. DOI: 10.1172/JCI118709. View

17.

Rautou P, Leroyer A, Ramkhelawon B, Devue C, Duflaut D, Vion A . Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circ Res. 2010; 108(3):335-43. DOI: 10.1161/CIRCRESAHA.110.237420. View

18.

Chanda M, Nantakomol D, Suksom D, Palasuwan A . Cell-derived microparticles after exercise in individuals with G6PD Viangchan. Clin Hemorheol Microcirc. 2014; 60(2):241-51. DOI: 10.3233/CH-141865. View

19.

Veitch S, Njock M, Chandy M, Siraj M, Chi L, Mak H . MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes. Cardiovasc Diabetol. 2022; 21(1):31. PMC: 8876371. DOI: 10.1186/s12933-022-01458-z. View

20.

Guiraud T, Gayda M, Juneau M, Bosquet L, Meyer P, Theberge-Julien G . A single bout of high-intensity interval exercise does not increase endothelial or platelet microparticles in stable, physically fit men with coronary heart disease. Can J Cardiol. 2013; 29(10):1285-91. DOI: 10.1016/j.cjca.2013.03.024. View