Lysophospholipids in coronary artery and chronic ischemic heart disease.
OBJECTIVE
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.


RESULTS
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, which 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.


CONCLUSIONS
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.
aDepartment of Veterans Affairs Medical Center bDivision of Cardiovascular Medicine, The Gill Heart Institute cUniversity of Kentucky, Lexington, Kentucky, USA.
Ahmed
A
Abdel-Latif
Paula M
PM
Heron
Andrew J
AJ
Morris
Susan S
SS
Smyth
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C032881:lysophosphatidic acid