Angiotensin II prevents the metabolic but not the transdifferentiating effect of EGF on vascular smooth muscle cells from human female donors.

Vascular smooth muscle cells (VSMCs) are at the center of vascular diseases but studies on VSMCs from human females are rare and the medical need for female-specific vascular research is urgent. VSMCs are simultaneously subjected to paracrine and autocrine mediators, whose effects do not simply add up. For instance, a synergistic crosstalk occurs between the VSMC epidermal growth factor receptor (EGFR), a major transducer of autocrine signals (membrane-derived EGF), and the paracrine angiotensin II (AngII) type 1 receptor (AT1R). Here, we investigated the effects of EGF and AngII on primary human VSMCs from female donors. EGF initiates VSMC transdifferentiation toward a proliferative and inflammatory phenotype and affects glucose and lipid metabolisms. Co-exposure with AngII does not affect the EGF-induced transdifferentiation but counteracts the metabolic effects, independently of AT1R. Activation of the MAS1 receptor by angiotensin 1-7, an AngII-cleavage product, mimicked the AngII effects. Similar EGF-AngII interactions were not observed in male VSMCs.