Ceramides and cardiovascular disease

Česká verzia

Authors: Ján Murín
Authors place of work: I. interná klinika LF UK a UNB, Nemocnica Staré Mesto, Bratislava
Published in the journal: Diab Obez 2023; 23(45): 29-33
Category: Reviews

Summary

Obesity is associated with an increased cardiovascular risk and therefore the knowledge of a potential role of dysregulations in the adipose tissues (AT) seems to be important. A study looking at metabolites (ceramides, sfingomyelins, free fatty acids, other) secreted by intrathoracic and subcutaneous AT in obese patients with atherosclerosis was conducted, and some of these patients were undergoing coronary bypass surgery. The underlying mechanisms were explored in human endothelial cells and their clinical value was tested against hard clinical endpoints. The intrathoracic AT volume is associated significantly with arterial oxidative stress and there are significant differences in sphingolipid secretion between intrathoracic AT and subcutaneous AT. C16:0-ceramide and its derivatives are the most abundant species released within adipocyte-derived extracellular vesicles. High intrathoracic AT sphingolipid secretion was significantly associated with reduced endothelial NO bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with intrathoracic AT production of ceramides, dysregulated vascular redox signaling and increased systemic inflammation in patients with atherosclerosis. High plasma C16:0-ceramide is independently related with increased risk for cardiac mortality. In a randomized controlled clinical trial, 1-year treatment of obese patients with the GLP-1 RA (liraglutid) supressed plasma C16:0-ceramide and C16:0-glycosylceramide. These results demonstrate for the 1st time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity and with an impact on cardiac mortality in advanced atherosclerosis.

Keywords:

vascular inflammation – Atherosclerosis – cardiovascular disease – adipose tissues – ceramides – intrathoracic adipose tissue– liraglutide

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