A red blood cell-derived lipid maintains blood pressure and cardiac function.

What is it about?

Sphingosine 1-phosphate (S1P) is a red blood cell-derived lipid that circulates in plasma bound to high-density lipoproteins (HDL) and albumin. By binding to receptors on vascular endothelial cells forming their inner lining, S1P is known to signal the stabilization of newly formed blood vessels, the sealing of barriers in leaky vessels and the dilation of arteries when exposed to increased blood flow. We studied mice that lack S1P in red blood cells and plasma, and report that blood-borne S1P also maintains peripheral vascular resistance, blood pressure, and cardiac contractile function. While still able to preserve cardiac output in a resting state, mice lacking plasma S1P fail to increase cardiac output when stressed. S1P bound to HDL is known to promote S1P receptor activation on vascular endothelial cells and thereby favor arterial dilation and blood pressure reduction. Our observations indicate that S1P that is bound to other plasma carriers, mainly albumin, plays an opposing role by promoting vascular resistance via activation of S1P receptors on smooth muscle cells in the blood vessel wall.

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Photo by Marek Piwnicki on Unsplash

Photo by Marek Piwnicki on Unsplash

Why is it important?

A number of recent studies have measured levels of S1P and its plasma carriers in plasma and serum of patients at risk of or suffering from cardiovascular disease or shock associated with systemic inflammation, some of which have reported significant correlations between S1P levels and disease severity or outcome. However, it remains unclear whether observed alterations in S1P levels are likely to impact vascular or cardiac function, and to what extent the distribution of S1P between its plasma carriers matters for its physiological activities. Our observation that genetic elimination of plasma S1P reduces resting blood pressure and cardiac contractile function in mice supports the notion that S1P could be more than a biomarker of disease severity. Contrasts between the effects of genetic elimination of all plasma S1P in our study and those of selective loss of HDL-bound S1P in previous studies also supports the relevance of observations that plasma carriers can dictate biological functions of S1P, emphasizing the potential diagnostic value of distinguishing between carrier-bound S1P pools.

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