[Leukotrienes: potential therapeutic targets in cardiovascular diseases].
Leukotrienes are potent inflammatory mediators synthesized locally within the cardiovascular system through the 5-lipoxygenase pathway of arachidonic acid metabolism. The leukotrienes, consisting of dihydroxy leukotriene LTB4 and the cysteinyl leukotrienes LTC4, LTD4 and LTE4, act by targeting cell surface receptors expressed on inflammatory cells and on structural cells of vessel walls. LTB, induces leukocyte activation and chemotaxis via high- and low-affinity receptor subtypes (BLT1 and BLT2), respectively. Recently, BLT, receptors were found on human vascular smooth muscle cells, inducing their migration and proliferation. Cysteinyl leukotrienes are vasoconstrictors and induce endothelium-dependent vascular responses through the CysLT, and CysLT2 receptor subtypes. There is also pharmacological evidence for the existence of further CysLT receptor subtypes. Taken together, experimental and genetic studies suggest a major role of leukotrienes in atherosclerosis and in its ischemic complications such as acute coronary syndromes and stroke. Furthermore, the effects on vascular smooth muscle cells suggest a role in the vascular remodeling observed after coronary angioplasty, as well as in aortic aneurysm. Further experimental and clinical studies are needed to determine the potential of therapeutic strategies targeting the leukotriene pathway in cardiovascular disease.
Bäck
Magnus
M
INSERM unité 698, CHU Xavier-Bichat, 16 rue Henri Huchard, 75018 Paris.
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001014:Aortic Aneurysm / Q000209:etiology / Q000503:physiopathology; D016718:Arachidonic Acid / Q000378:metabolism; D050197:Atherosclerosis / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D002465:Cell Movement; D023903:Coronary Restenosis / Q000503:physiopathology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000378:metabolism / Q000502:physiology; D017997:Leukotriene C4 / Q000378:metabolism / Q000502:physiology; D017998:Leukotriene D4 / Q000378:metabolism / Q000502:physiology; D017999:Leukotriene E4 / Q000378:metabolism / Q000502:physiology; D015289:Leukotrienes / Q000097:blood / Q000378:metabolism / Q000502:physiology* / Q000652:urine; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D051381:Rats; D018077:Receptors, Leukotriene / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018077:Receptors, Leukotriene; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D017998:Leukotriene D4; D017999:Leukotriene E4