The stellate vascular smooth muscle cell phenotype is induced by IL-1ß via the secretion of PGE2 and subsequent cAMP-dependent protein kinase A activation.

Biochimica et biophysica acta

PubMedID: 26403276

Blirando K, Blaise R, Gorodnaya N, Rouxel C, Meilhac O, Vincent P, Limon I. The stellate vascular smooth muscle cell phenotype is induced by IL-1ß via the secretion of PGE2 and subsequent cAMP-dependent protein kinase A activation. Biochim Biophys Acta. 2015;.
Atherosclerosis development is associated with morphological changes to intimal cells, leading to a stellate cell phenotype. In this study, we aimed to determine whether and how key pro-atherogenic cytokines present in atherosclerotic plaques (IL-1ß, TNFa and IFN?) could induce this phenotype, as these molecules are known to trigger the transdifferentiation of vascular smooth muscle cells (VSMCs). We found that, IL-1ß was the only major inflammatory mediator tested capable of inducing a stellate morphology in VSMCs. This finding was confirmed by staining for F-actin and vinculin at focal adhesions, as these two markers were disrupted only by IL-1ß. We then investigated the possible association of this IL-1ß-dependent change in morphology with an increase in intracellular cAMP concentration ([cAMP]), using the FRET-based biosensor for cAMP (T)Epac(VV). EXPERIMENTS
in the presence of IL-1ß or medium conditioned by IL-1ß-treated VSMCs and pharmacological tools demonstrated that the long-term increase in intracellular cAMP concentration was induced by the secretion of an autocrine/paracrine mediator, prostaglandin E2 (PGE2), acting through the EP4 receptor.Finally, by knocking down the expression of the regulatory subunit PKAR1a, thereby reproducing the effects of IL-1ß and PGE2 on VSMCs, we demonstrated the contribution of PKA activity to the observed behavior of VSMCs.