Figure 7.

Schematic model of mechanical strain responses in IMA and SV SMCs. A: IMA-SMCs remain quiescent when exposed to stretch, which corresponds with relatively high p27^Kip1 protein expression levels and unaffected proliferation. B: In SV-SMCs, integrin signaling is activated in response to mechanical strain resulting in down-regulation of p27^Kip1 protein expression and induction of proliferation. Simultaneously, feedback mechanisms are initiated in SV-SMCs involving enhanced TR3 expression to prevent an excessive proliferative response. C: The importance of TR3 in such endogenous inhibitory pathways has been revealed by knocking down TR3 expression (siRNA), which results in enhanced proliferation of SV-SMCs after mechanical strain. D: Overexpression of TR3 or enhancement of the activity of endogenous TR3 with the agonist 6-MP results in a reduction of stretch-induced proliferation.