Thanks to both internal (Pandolfi and Consoli research Groups) and external collaborations (V. Trischitta and G. Sesti, Rome Sapienza University and M. Federici, Rome Tor Vergata University), the HUVECs Research Biobank currently includes about 1000 strains of Human Umbilical Vein Endothelial Cells obtained from umbilical cords of healthy pregnant women (Control-HUVECs, C-HUVECs) and about 200 strains obtained from umbilical cords of women suffering from Gestational Diabetes (Gestational Diabetes- HUVECs, GD-HUVECs). The clinical characteristics of the donor are available for most strains.
As to GD-HUVECs strains, these human endothelial cells have been exposed in vivo, even transiently, to hyperglycaemia, oxidative stress and inflammation and exhibit durable pro-atherogenic modifications. They indeed retain a ‘diabetic cardiovascular phenotype’ even after lengthy in vitro exposure to physiological glucose concentrations, compatible with in vivo hyperglycaemia induced epigenetic modifications exerting control of gene expression. This would be consistent with clinical data gathered in large outcome trials on diabetic patients also pointing to the existence of a hyperglycaemia related ‘metabolic legacy’(Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus? Coco C, Sgarra L, Potenza MA, Nacci C, Pasculli B, Barbano R, Parrella P, Montagnani M. Int J Mol Sci. 2019 Jun 17;20(12):2949. doi: 10.3390/ijms20122949).
Key References
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- Di Fulvio P., Pandolfi A., Formoso G., Di Silvestre S., Di Tomo P., Giardinelli A., De Marco A., Di Pietro N., Taraborrelli M., Sancilio S., Di Pietro R., Piantelli M., Consoli A. “Features of endothelial dysfunction in gestational diabetic women umbilical cord vessels”. Nutr Metab Cardiovasc Dis. 2014 Dec; 24(12):1337-45. DOI: 10.1016/j.numecd.2014.06.005.
- Di Tomo P., Di Silvestre S., Cordone V.G.P., Giardinelli A., Faricelli B., Pipino C., Lanuti P., Peng T., Formoso G., Yang D., Arduini A., Chiarelli F., Pandolfi A. and Di Pietro N. Centella Asiatica and Lipoic Acid, or a combination thereof, inhibit monocyte adhesion to endothelial cells from umbilical cords of gestational diabetic women. Nutr Metab Cardiovasc Dis. 2015 Jul; 25(7):659-66. DOI: 10.1016/j.numecd.2015.04.002.
- Di Tomo P., Lanuti P., Di Pietro N., Baldassarre M.P.A., Marchisio M., Pandolfi A., Consoli A., Formoso G., Liraglutide Mitigates TNF-α Induced Pro-Atherogenic Changes and Microvesicle Release in HUVEC From Diabetic Women. Diabetes Metab Res Rev. 2017 Nov;33(8). Epub 2017 Sep 6. DOI: 10.1002/dmrr.2925.
- Ucci M., Di Tomo P., Tritschler F., Cordone V. G. P., Lanuti P., Bologna G., Di Silvestre S., Di Pietro N., Pipino C., Mandatori D., Formoso G., Pandolfi A. Anti-inflammatory Role of Carotenoids in Endothelial Cells Derived from Umbilical Cord of Women Affected by Gestational Diabetes Mellitus. Oxid Med Cell Longev. 2019 Jan 30; 2019:8184656. DOI: 10.1155/2019/8184656.
Insulin resistance alters metabolic and vascular homeostasis as well as endothelial function. Thus, it is a major contributor to atherosclerosis. Ample evidence exists that several genetic variants (G972R, ENPP1, TRB3, GRB14, etc) confer increased risk of both insulin resistance and of cardiovascular complications development. Insulin resistance-related mechanisms might concur to the association between these variants and increased cardiovascular risk.
Our in vitro studies performed in HUVECs naturally carrying one or more of these variants, a model uniquely suited to investigate the direct effects of the gene variants on human endothelium, provide novel insights on the molecular mechanisms of this association.
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- Federici M., Pandolfi A., De Filippis E.A., Pellegrini G., Menghini R., Lauro D., Cardellini M., Romano M., Sesti G., Lauro R., Consoli A., G972R IRS-1 Variant Impairs Insulin Regulation of Endothelial Nitric Oxide Synthase in Cultured Human Endothelial Cells. Circulation. 2004 Jan 27;109(3):399-405. Epub 2004 Jan 5. DOI: 10.1161/01.CIR.0000109498.77895.6F.
- Andreozzi F., Formoso G., Prudente S., Hribal M.L., Pandolfi A., Bellacchio E., Di Silvestre S., Trischitta V., Consoli A., Sesti G.TRIB3 R84 variant is associated with impaired insulin-mediated nitric oxide production in human endothelial cells. Arterioscler Thromb Vasc Biol. 2008 Jul; 28(7):1355-60. DOI: 10.1161/ATVBAHA.108.162883.
- Bacci S., Di Paola R., Menzaghi C., Di Fulvio P., Di Silvestre S., Pellegrini F., Baratta R., Marucci A., Mastroianno S., Fini G., Formoso G., Consoli A., Perticone F., Frittitta L., Pandolfi A., Trischitta V. ENPP1 Q121 variant, increased pulse pressure and reduced insulin signaling, and nitric oxide synthase activity in endothelial cells. Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1678-83. DOI: 10.1161/ATVBAHA.109.189191.
- Formoso G., Di Tomo P., Andreozzi F., Succurro E., Di Silvestre S., Prudente S., Perticone F., Trischitta V., Sesti G., Pandolfi A., Consoli A. The TRIB3 R84 variant is associated with increased carotid intima-media thickness in vivo and with enhanced MAPK signalling in human endothelial cells. Cardiovasc Res. 2011 Jan 1;89(1):184-92. Epub 2010 Aug 5. DOI: 10.1093/cvr/cvq255.
- Prudente S., Sesti G., Pandolfi A., Andreozzi F., Consoli A., Trischitta V. The mammalian tribbles homolog TRIB3, glucose homeostasis, and cardiovascular diseases. Endocr Rev. 2012 Aug;33(4):526-46. DOI: 10.1210/er.2011-1042.
