Sphingolipids and Atherosclerosis: The Dual Role of Ceramide and Sphingosine-1-Phosphate

被引:30
作者
Piccoli, Marco [1 ,2 ]
Cirillo, Federica [1 ,2 ]
Ghiroldi, Andrea [1 ,2 ]
Rota, Paola [2 ,3 ]
Coviello, Simona [1 ,2 ]
Tarantino, Adriana [1 ,2 ,4 ]
La Rocca, Paolo [2 ,5 ]
Lavota, Ivana [1 ,2 ]
Creo, Pasquale [1 ,2 ]
Signorelli, Paola [2 ,6 ]
Pappone, Carlo [2 ,4 ,7 ]
Anastasia, Luigi [1 ,2 ,4 ]
机构
[1] IRCCS Policlin San Donato, Lab Stem Cells Tissue Engn, Piazza Malan 2, I-20097 Milan, Italy
[2] Inst Mol & Translat Cardiol IMTC, San Donato Milanese, I-20097 Milan, Italy
[3] Univ Milan, Dept Biomed Surg & Dent Sci, I-20133 Milan, Italy
[4] Univ V Salute San Raffaele, Fac Med & Surg, Via Olgettina 58, I-20132 Milan, Italy
[5] Univ Milan, Dept Biomed Sci Hlth, Via Mangiagalli 31, I-20133 Milan, Italy
[6] Univ Milan, Aldo Ravelli Ctr Neurotechnol & Expt Brain Therape, Dept Hlth Sci, Via Antonio Rudini 8, I-20142 Milan, Italy
[7] IRCCS Policlin San Donato, Arrhythmol Dept, Piazza Malan 2, I-20097 Milan, Italy
关键词
atherosclerosis; coronary artery disease (cad); sphingolipids; ceramide; sphingosine-1-phosphate; oxidative stress; endothelial dysfunction; atherosclerotic plaque; LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; PROTEIN-COUPLED RECEPTOR; LONG-CHAIN CERAMIDES; SPHINGOSINE; 1-PHOSPHATE; ENDOTHELIAL-CELLS; ACID SPHINGOMYELINASE; OXIDATIVE STRESS;
D O I
10.3390/antiox12010143
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sphingolipids are bioactive molecules that play either pro- and anti-atherogenic roles in the formation and maturation of atherosclerotic plaques. Among SLs, ceramide and sphingosine-1-phosphate showed antithetic properties in regulating various molecular mechanisms and have emerged as novel potential targets for regulating the development of atherosclerosis. In particular, maintaining the balance of the so-called ceramide/S1P rheostat is important to prevent the occurrence of endothelial dysfunction, which is the trigger for the entire atherosclerotic process and is strongly associated with increased oxidative stress. In addition, these two sphingolipids, together with many other sphingolipid mediators, are directly involved in the progression of atherogenesis and the formation of atherosclerotic plaques by promoting the oxidation of low-density lipoproteins (LDL) and influencing the vascular smooth muscle cell phenotype. The modulation of ceramide and S1P levels may therefore allow the development of new antioxidant therapies that can prevent or at least impair the onset of atherogenesis, which would ultimately improve the quality of life of patients with coronary artery disease and significantly reduce their mortality.
引用
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页数:30
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