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Activation of sphingosine-1-phosphate signalling as a potential underlying mechanism of the pleiotropic effects of statin therapy.

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Academic year: 2021

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Activation of sphingosine-1-phosphate

signalling as a potential underlying

mechanism of the pleiotropic effects of

statin therapy

Abstract

The mechanisms by which statins are beneficial are incompletely understood. While the lowering of low-density lipoprotein concentration is associated with regression of

atherosclerosis, the observed benefit of statin therapy begins within months after its initiation, making regression an unlikely cause. Although LDL-C lowering is the main mechanism by which statin therapy reduces cardiovascular events, evidence suggests that at least some of the beneficial actions of statins may be mediated by their pleiotropic effects. Thus, statins may modulate the function of cardiovascular cells and key signalling proteins, including small G-proteins, to ultimately exert their pleiotropic effects. Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lysophospholipid that regulates diverse physiological functions in a variety of different organ systems. Within the cardiovascular system, S1P mediates cardioprotection following ischemia/reperfusion injury, anti-inflammatory response,

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