Journal
BIOMEDICINES
Volume 9, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines9010018
Keywords
diabetes; hyperglycemia; glycated lipoproteins; glycated LDL; glycated HDL; endothelial cell dysfunction; molecular mechanisms; epigenetic factors; therapeutic approaches
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Funding
- Romanian Ministry of National Education [41-067/2007]
- PN-II-PT-PCCA-2011-3.1-0184 project [PCCA-127/2012]
- PN-II-RU-TE-2014-4-0506 project [TE 11/2015]
- Romanian Academy
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Studies have shown that diabetes and its vascular complications are related to endothelial cell dysfunction, leading to cardiovascular diseases as the main cause of death and disability in diabetic patients. Through the action of high blood sugar and advanced glycation end products, EC dysfunction is induced, affecting endothelial cells and exacerbating vascular complications.
Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.
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