Pharmacological Elevation of Circulating Bioactive Phosphosphingolipids Enhances Myocardial Recovery After Acute Infarction

Klyachkin, Yuri M.; Nagareddy, Prabhakara R; Ye, Shaojing; Wysoczynski, Marcin; Asfour, Ahmed; Gao, Erhe; Sunkara, Manjula; Brandon, Ja A.; Annabathula, Rahul; Ponnapureddy, Rakesh; Solanki, Matesh; Pervaiz, Zahida Hassan; Smyth, Susan S.; Ratajczak, Mariusz Z.; Morris, Andrew J.; Abdel‐Latif, Ahmed

doi:10.5966/sctm.2014-0273

Cited by 25 publications

(31 citation statements)

References 49 publications

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“…Indeed, overexpression of SPHK1 to rescue the decreased production of S1P in the heart reduces the infarct size and preserves the cardiac function (65). Furthermore, inhibition of S1P lyase to increase the plasma level of S1P also reduces the infarct size and enhances the recovery of cardiac function in vivo (66), which is consistent with the results from the study using ex vivo heart (54). Inhibition of S1P lyase to increase the plasma level of S1P is accompanied by increased number of bone marrow-derived stem cells in the circulation, indicating that S1P-induced mobilization of bone marrow-derived stem cells may also contribute to the protective effect of S1P (66).…”

Section: S1p Signaling In Heartsupporting

confidence: 88%

“…Furthermore, inhibition of S1P lyase to increase the plasma level of S1P also reduces the infarct size and enhances the recovery of cardiac function in vivo (66), which is consistent with the results from the study using ex vivo heart (54). Inhibition of S1P lyase to increase the plasma level of S1P is accompanied by increased number of bone marrow-derived stem cells in the circulation, indicating that S1P-induced mobilization of bone marrow-derived stem cells may also contribute to the protective effect of S1P (66). Contrary to the previous study showing no cardioprotective effect of FTY720 in vivo , a more recent study, however, demonstrated that post-conditioning with FTY720 reduces infarct volume and improves short-term and long-term hemodynamic outcome (67).…”

Section: S1p Signaling In Heartsupporting

confidence: 88%

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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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Section: S1p Signaling In Heartsupporting

confidence: 88%

Section: S1p Signaling In Heartsupporting

confidence: 88%

Implication of sphingosin-1-phosphate in cardiovascular regulation

Zhang

2016

Front Biosci

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“…Reduced levels of plasma S1P have been also reported in patients affected by coronary artery diseases and they inversely correlate with the severity of the diseases[77, 78]. In spite of discordant changes in plasma S1P following MI in preclinical studies[73, 79, 80], administration of HDL and S1P to the mice protected the heart from ischemia reperfusion injury [81], underlining a cardioprotective function of S1P signaling.…”

Section: Sphingolipid De Novo Pathway and S1p In The Heartmentioning

confidence: 99%

Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis

Sasset

Zhang

Dunn

et al. 2016

Trends in Endocrinology & Metabolism

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Sphingolipids are both, fundamental structural components of the eukaryotic membranes and signaling molecules regulating a variety of biological functions. Highly bioactive lipids, ceramide and sphingosine-1-phosphate have emerged as important regulators of cardiovascular functions in health and disease. In this review we discuss recent insights into the role of sphingolipids, particularly ceramide and sphingosine-1-phosphate, in the pathophysiology of the cardiovascular system. We also highlight advances into the molecular mechanisms regulating serine palmitoyltransferase, the first and rate-limiting enzyme of de novo biosynthesis, with an emphasis on recently discovered inhibitors of serine palmitoyltransferase, ORMDL and NOGO-B proteins. Understanding the molecular mechanisms regulating this biosynthetic pathway may lead to the development of novel therapeutic approaches for the treatment of cardiovascular diseases.

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“…Plasma, obtained from AMI patients at times that correlate with both peak S1P levels and mobilized stem cells, stimulates BMSPC migration in an S1P 1 receptor-dependent manner [48]. Moreover, the inhibition of S1P lyase augments S1P-mediated mobilization of BMSPCs after MI and enhances angiogenesis, cardiomyocyte proliferation and cardiac functional recovery in animal models [53]. Taken together these findings highlight the importance of bioactive lipids and complement cascade in the mobilization and homing of BMSPCs to the ischemic myocardium.…”

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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Pharmacological Elevation of Circulating Bioactive Phosphosphingolipids Enhances Myocardial Recovery After Acute Infarction

Cited by 25 publications

References 49 publications

Implication of sphingosin-1-phosphate in cardiovascular regulation

Implication of sphingosin-1-phosphate in cardiovascular regulation

Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis

Lysophospholipids in coronary artery and chronic ischemic heart disease

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