SKI-II – a sphingosine kinase 1 inhibitor – exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R−/−) mice on high cholesterol diet

Potì, Francesco; Ceglarek, Uta; Burkhardt, Ralph; Simoni, Manuela; Nofer, Jerzy–Roch

doi:10.1016/j.atherosclerosis.2015.03.020

Cited by 41 publications

(29 citation statements)

References 24 publications

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“…Thus, in mice, sphingosine kinase 2 inhibition reduced both plasma S1P and triglycerides (Poti et al, 2012;Potì et al, 2015), whereas S1P-lyase deficiency increased plasma S1P and triglycerides (Bektas et al, 2010). Moreover, FTY720 accelerates lipolysis in vitro (Moon et al, 2012), implying direct effects of S1P on adipocyte biology.…”

Section: Discussionmentioning

confidence: 97%

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

et al. 2018

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ArticleThe Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity SUMMARYApolipoprotein M (apoM) is the carrier of sphingosine-1-phosphate (S1P) in plasma high-density lipoproteins. S1P is a bioactive lipid interacting with five receptors (S1P 1-5 ). We show that lack of apoM in mice increases the amount of brown adipose tissue (BAT), accelerates the clearance of postprandial triglycerides, and protects against diet-induced obesity (i.e., a phenotype similar to that induced by cold exposure or b 3 -adrenergic stimulation). Moreover, the data suggest that the phenotype of apoM-deficient mice is S1P dependent and reflects diminished S1P 1 stimulation. The results reveal a link between the apoM/S1P axis and energy metabolism.

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Section: Discussionmentioning

confidence: 97%

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

et al. 2018

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“…The atheroprotective role of S1P is also supported by studies that manipulate S1P levels by targeting S1P metabolic enzymes. SPHK1 inhibitor that significantly reduced plasma S1P levels increases atherosclerotic lesions in LDL receptor KO mice (98), whereas deficiency of S1P lyase, an enzyme that degrades S1P, decreases atherosclerotic lesion in LDL receptor KO Mice (99). …”

Section: S1p Signaling In Vasculaturementioning

confidence: 99%

Implication of sphingosin-1-phosphate in cardiovascular regulation

Zhang

2016

Front Biosci

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Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite generated by phosphorylation of sphingosine catalyzed by sphingosine kinase. S1P acts mainly through its high affinity G-protein-coupled receptors and participates in the regulation of multiple systems, including cardiovascular system. It has been shown that S1P signaling is involved in the regulation of cardiac chronotropy and inotropy and contributes to cardioprotection as well as cardiac remodeling; S1P signaling regulates vascular function, such as vascular tone and endothelial barrier, and possesses an anti-atherosclerotic effect; S1P signaling is also implicated in the regulation of blood pressure. Therefore, manipulation of S1P signaling may offer novel therapeutic approaches to cardiovascular diseases. As several S1P receptor modulators and sphingosine kinase inhibitors have been approved or under clinical trials for the treatment of other diseases, it may expedite the test and implementation of these S1P-based drugs in cardiovascular diseases.

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“…In hyperlipidemic mice, development of atherosclerosis appears to be inversely proportional to S1P levels. For example, reducing S1P production by SK2 inhibition promotes the development of atherosclerosis [25]; whereas, an inhibitor of S1P lyase, which increases S1P, attenuates the development of atherosclerosis [26]. The S1P 1 receptor may be responsible for these anti-atherosclerotic effects because S1P 1 agonism reduces atherosclerosis [27].…”

Section: Sphingolipids In Chronic Ischemic Heart Diseasementioning

confidence: 99%

Lysophospholipids in coronary artery and chronic ischemic heart disease

Abdel‐Latif

Heron

Morris

et al. 2015

Current Opinion in Lipidology

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Purpose of review The bioactive lysophospholipids, lysophosphatidic acid (LPA) and sphingosine 1 phosphate (S1P) have potent effects on blood and vascular cells. This review focuses their potential contributions to the development of atherosclerosis, acute complications, such as acute myocardial infarction, and chronic ischemic cardiac damage. Recent findings Exciting recent developments have provided insight into the molecular underpinnings of LPA and S1P receptor signaling. New lines of evidence suggest roles for these pathways in the development of atherosclerosis. In experimental animal models, the production, signaling and metabolism of LPA may be influenced by environmental factors in the diet that synergize to promote the progression of atherosclerotic vascular disease. This is supported by observations of human polymorphisms in the lysophospholipid metabolizing enzyme, PPAP2B, that are associated with risk of coronary artery disease and myocardial infarction. S1P signaling protects from myocardial damage that follows acute and chronic ischemia both by direct effects on cardiomyocytes and through stem cell recruitment to ischemic tissue. Summary This review will suggest novel strategies to prevent the complications of coronary artery disease by targeting LPA production and signaling. Additionally, ways in which S1P signaling pathways may be harnessed to attenuate ischemia-induced cardiac dysfunction will be explored.

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SKI-II – a sphingosine kinase 1 inhibitor – exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R−/−) mice on high cholesterol diet

Cited by 41 publications

References 24 publications

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

Implication of sphingosin-1-phosphate in cardiovascular regulation

Lysophospholipids in coronary artery and chronic ischemic heart disease

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