ACTA2 and pulmonary arterial hypertension: There was also a non-monotonic response to the two levels of increased substrate stiffness in the expression of Loxl1 and Acta2, which were both upregulated compared with 0.5 kPa substrates on 3 kPa matrices (similar to vessel walls during mild PAH), but the expression of both was not significantly altered compared with 0.5 kPa substrates on 10 kPa matrices (which are comparable in stiffness to vessel walls during severe PAH).