Ceramides and other sphingolipids as drivers of cardiovascular disease.
Journal
Nature reviews. Cardiology
ISSN: 1759-5010
Titre abrégé: Nat Rev Cardiol
Pays: England
ID NLM: 101500075
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
accepted:
22
02
2021
pubmed:
28
3
2021
medline:
22
1
2022
entrez:
27
3
2021
Statut:
ppublish
Résumé
Increases in calorie consumption and sedentary lifestyles are fuelling a global pandemic of cardiometabolic diseases, including coronary artery disease, diabetes mellitus, cardiomyopathy and heart failure. These lifestyle factors, when combined with genetic predispositions, increase the levels of circulating lipids, which can accumulate in non-adipose tissues, including blood vessel walls and the heart. The metabolism of these lipids produces bioactive intermediates that disrupt cellular function and survival. A compelling body of evidence suggests that sphingolipids, such as ceramides, account for much of the tissue damage in these cardiometabolic diseases. In humans, serum ceramide levels are proving to be accurate biomarkers of adverse cardiovascular disease outcomes. In mice and rats, pharmacological inhibition or depletion of enzymes driving de novo ceramide synthesis prevents the development of diabetes, atherosclerosis, hypertension and heart failure. In cultured cells and isolated tissues, ceramides perturb mitochondrial function, block fuel usage, disrupt vasodilatation and promote apoptosis. In this Review, we discuss the body of literature suggesting that ceramides are drivers - and not merely passengers - on the road to cardiovascular disease. Moreover, we explore the feasibility of therapeutic strategies to lower ceramide levels to improve cardiovascular health.
Identifiants
pubmed: 33772258
doi: 10.1038/s41569-021-00536-1
pii: 10.1038/s41569-021-00536-1
pmc: PMC8978615
mid: NIHMS1789338
doi:
Substances chimiques
Ceramides
0
Sphingolipids
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
701-711Subventions
Organisme : NIDDK NIH HHS
ID : T32 DK110966
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115824
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK131609
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130296
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141540
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122001
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK091317
Pays : United States
Informations de copyright
© 2021. Springer Nature Limited.
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