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Membrane and soluble endoglin role in cardiovascular and metabolic disorders related to metabolic syndrome

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Abstract

Membrane endoglin (Eng, CD105) is a transmembrane glycoprotein essential for the proper function of vascular endothelium. It might be cleaved by matrix metalloproteinases to form soluble endoglin (sEng), which is released into the circulation. Metabolic syndrome comprises conditions/symptoms that usually coincide (endothelial dysfunction, arterial hypertension, hyperglycemia, obesity-related insulin resistance, and hypercholesterolemia), and are considered risk factors for cardiometabolic disorders such as atherosclerosis, type II diabetes mellitus, and liver disorders. The purpose of this review is to highlight current knowledge about the role of Eng and sEng in the disorders mentioned above, in vivo and in vitro extent, where we can find a wide range of contradictory results. We propose that reduced Eng expression is a hallmark of endothelial dysfunction development in chronic pathologies related to metabolic syndrome. Eng expression is also essential for leukocyte transmigration and acute inflammation, suggesting that Eng is crucial for the regulation of endothelial function during the acute phase of vascular defense reaction to harmful conditions. sEng was shown to be a circulating biomarker of preeclampsia, and we propose that it might be a biomarker of metabolic syndrome-related symptoms and pathologies, including hypercholesterolemia, hyperglycemia, arterial hypertension, and diabetes mellitus as well, despite the fact that some contradictory findings have been reported. Besides, sEng can participate in the development of endothelial dysfunction and promote the development of arterial hypertension, suggesting that high levels of sEng promote metabolic syndrome symptoms and complications. Therefore, we suggest that the treatment of metabolic syndrome should take into account the importance of Eng in the endothelial function and levels of sEng as a biomarker and risk factor of related pathologies.

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Funding

This work was supported by project EFSA-CDN (No. CZ.02.1.01/0.0/0.0/16_019/0000841) co-funded by ERDF, Specific University Research (SVV 260 549), Charles University Grant Agency, GAUK 1130120/C, GAUK 1166119/C, and AZV CZ No. 17-31754A.

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Vicen, M., Igreja Sá, I.C., Tripská, K. et al. Membrane and soluble endoglin role in cardiovascular and metabolic disorders related to metabolic syndrome. Cell. Mol. Life Sci. 78, 2405–2418 (2021). https://doi.org/10.1007/s00018-020-03701-w

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