Lim domain containing proteins among them Crp2 play a central role in organogenesis and cellular differentiation. Crp2 is specifically expressed in cardiovascular tissue. Its up-regulation in cardiomyocytes coincides with vascular smooth muscle differentiation. Therefore the role of Crp2 in cardiac remodelling was addressed in Crp2^-/- mice under chronic elevation of left ventricular afterload in vivo. Furthermore, vascular contractility of these mice was characterized in vitro.

Transverse aortic constriction (TAC) was induced in wild type (WT) and Crp2^-/- mice. After 14 days cardiac function was monitored by cardiac catheterisation. Cardiac hypertrophy and fibrosis was evaluated by morphometric analysis. Phenylephrine and potassium induced vascular contraction as well as endothelially mediated relaxation were recorded in WT and Crp2^-/- mice in a Mulvany myograph.

14 days after TAC Crp2^-/- animals developed exacerbated cardiac hypertrophy and moderate myocardial fibrosis compared to the WT group. This was supported by more severe elevation of blood pressure in Crp2^-/- mice. At the same time the pressure gradient across the stenosis was comparable in both, WT and Crp2^-/- mice. Functional analysis of cardiac contraction revealed an acute diastolic dysfunction and reduced contractile reserve in Crp2^-/- mice. Aortic rings of Crp2^-/- displayed enhanced vascular contraction under stimulation with phenylephrine or increased extracellular potassium. Endothelially mediated relaxation was unaffected by Crp2 deficiency.

TAC induced cardiac hypertrophy develops to a higher extent in Crp2^-/- animals. This is supported an aggravated vascular contraction in vitro. Crp2 plays a central role in cardiac and vascular homoeostasis, its loss leads to disturbed cardiac remodelling.