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Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
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Sphingolipids in Atherosclerosis: Chimeras in Structure and Function.

Lisa Peters1,2,3, Wolfgang M Kuebler1,2,4,5, Szandor Simmons1,2

  • 1Institute of Physiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.

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|October 14, 2022
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Summary

Sphingolipids play a complex role in atherosclerosis, a leading cause of death. Understanding their dual functions is key to developing new treatments for this inflammatory vascular disease.

Keywords:
atherosclerosiscardiovascular diseaseceramidedihydrocerammideglucosylceramidelactosylceramidesphingolipidssphingomyelinsphingosine-1-phosphate

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Area of Science:

  • Cardiovascular Research
  • Lipid Metabolism
  • Inflammatory Diseases

Background:

  • Atherosclerosis is a major global health issue, causing significant mortality and morbidity.
  • It involves arterial plaque formation, leading to events like stroke and heart attack.
  • Understanding cellular and molecular mechanisms is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To review the specific roles of six common sphingolipids in atherosclerosis.
  • To focus on cell types, molecules, enzymes, and receptors involved in atherogenesis.
  • To highlight the dual, or 'chimeric,' functions of certain sphingolipids in disease progression.

Main Methods:

  • Review of existing literature on sphingolipids and atherosclerosis.
  • Analysis of the roles of dihydroceramide (DhCer), ceramide (Cer), sphingosine-1-phosphate (S1P), sphingomyelin (SM), lactosylceramide (LacCer), and glucosylceramide (GluCer).
  • Focus on cellular and molecular players within the sphingolipid pathway.

Main Results:

  • Six common sphingolipids (DhCer, Cer, S1P, SM, LacCer, GluCer) are found in atherosclerotic plaques.
  • GluCer and LacCer are generally associated with atheroprotective effects.
  • DhCer, Cer, SM, and S1P exhibit dual roles, potentially promoting or protecting against atherosclerosis.

Conclusions:

  • Sphingolipids have critical, multifaceted roles in the development of atherosclerosis.
  • Interventions targeting the sphingolipid pathway show promise in preventing atherosclerosis.
  • Future research must clarify the context-dependent functions of sphingolipids for effective therapeutic strategies.