Researchers have shown that ERα/β can directly bind, inhibit, and recruit protein degradation systems (by e.g. SMURF1) to SMAD2/3 in an oestrogen-dependent manner (Figure 4).145–148 BMP stimulated SMAD1/5/8 phosphorylation was also reduced by oestrogen treatment in the same non-vascular cell lines.149 To add complexity to this oestrogen-TGFβ crosstalk, SMADs can also be a cofactor for sex-hormone receptor-mediated transcription.150,151 Evidently, as these studies made use of non-vascular cells, there is a need to confirm their findings towards vascular biology in the context of PAH. The gene discussed is TGFB1; the disease is pulmonary arterial hypertension.