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Dysfunctional HDL in type 2 diabetes mellitus: A link between chronic inflammation and cardiovascular risk

Abstract:

HDL are a heterogeneous group of lipoproteins that have in common a high density and a small size compared to the other lipoproteins, and are coupled in the circulation with other proteins and lipids that are continuously exchanged. The main function of HDL is reverse cholesterol transport, as well as anti-oxidative, anti-inflammatory and anti-atherogenic functions, consecrating it as protective lipoprotein. However, the use of HDL-C for decades has shown to be a poor pbkp_redictor of cardiovascular disease in certain situations, suggesting that the quality of HDL is more important than its quantity. This is how the concept of dysfunctional HDL arises, being defined as the inability to carry out their beneficial functions and instead become pro-oxidative, pro-inflammatory and pro-atherogenic lipoproteins that contribute to the process of atherosclerosis. These alterations are of vital importance in diabetic patients, who have an elevated cardiovascular risk and present a classical atherogenic dyslipidemia, using the HDL-C concentration as a risk marker. The microenvironment of chronic inflammation, oxidative stress and chronic hyperglycemia causes structural alterations in Apo A-I, paraoxonase, LCAT, in the lipid composition of lipoprotein and other molecules that belong to its structure, leading to its dysfunction. It is necessary to know the molecular mechanisms that are behind these alterations, proposing new strategies for the treatment and monitoring of dyslipidemia in diabetic patients, approaching more specifically the relationship between HDL and cardiovascular risk.