FIG. 3.

In silico models can translate in vitro findings to the in vivo setting. For example, in vitro studies have shown that the phenotype of VSMCs is strongly influenced by Notch signaling and mechanics: (A) high Notch activation corresponds to contractile VSMCs; (B) cyclic strain downregulates the expression of Notch3 and Jag1, and low levels of Notch correspond to proliferative VSMCs. By accounting for the fact that (C) the strain in arteries decreases with wall thickness and, consequently, (D) Notch3 and Jag1 expression levels increase with arterial thickness, (E) a recent computational model⁴ predicted that Notch mechanosensitivity can induce a phenotypic switch of VSMCs from proliferative to contractile for a specific wall thickness, thereby suggesting a mechanism that regulates the arterial homeostatic thickness (A and B are adapted from Ref. Loerakker and Ristori⁸²).