Lipidomics by 1H-NMR of non-LDL atherogenic lipoproteins in patients with dyslipidemia. Impact on vascular and metabolic complications

Identifier:  TDX:4338

Handle: https://hdl.handle.net/20.500.11797/TDX4338

Authors:  Moreno Vedia, Juan

Abstract:
Triglyceride-rich lipoproteins (TRL) emerge as important pathogenic factors in the context of lipoprotein disorders. Increased levels are associated with increased cardiovascular risk due to their ability to penetrate the subendothelial space, contributing to cholesterol accumulation. This accumulation is attributed not only to their cholesterol content, but also to the deposition of other proinflammatory lipids. In situations characterized by atherogenic dyslipidemia, commonly observed in prevalent diseases such as obesity and type 2 diabetes (T2D), these lipoproteins also contribute to ectopic fat accumulation in peripheral tissues. During the development of this PhD thesis, we explored the use of proton nuclear magnetic resonance spectroscopy (1H-NMR) as a reliable and high-throughput technology to study the metabolomic and lipidomic profile of patients with hypertriglyceridemia at cardiometabolic risk. Following both cross-sectional and prospective approaches, we identified associations between TRL and glycoproteins (Glycs), as well as between low molecular weight metabolites (LMWM) and various biochemical and clinical parameters; these LMWM were also related to T2D. In addition, basal levels of Glycs were detected as potential predictors of metabolic-dysfunction associated steatotic liver disease (MASLD), and specific molecules such as alanine and valine emerged as potential predictors of atherosclerotic cardiovascular disease (ASCVD) in patients with T2D. We further delved into the relevance of the lipidomic composition of TRL, showing that particles with higher relative cholesterol content have greater cellular proinflammatory effects. In addition, we observed changes in TG and cholesterol content in different lipoprotein fractions measured in non-fasting plasma samples that could reflect the proatherogenic nature of the postprandial state.