The LIM-domain containing protein Fhl2 is specifically expressed within the cardiovascular system during ontogenesis and high expression levels continue throughout lifetime. Fhl2 acts intranuclearly as co-activator and -repressor of transcription factors. Fhl2 deficiency is known to induce an exacerbated cardiac hypertrophy upon chronic beta-adrenergic stimulation. This study investigates the influence of Fhl2 on cardiac remodelling caused by transverse aortic constriction (TAC).

TAC was induced in wildtype and Fhl2^-/- mice. After 14 days, morphometric and hemodynamic evaluations were performed. In other groups angiotensin was applied chronically in a pro-hypertrophic dose. Vascular contraction and relaxation was examined and renal renin-mRNA-expression was analysed by qrt-PCR.

TAC induced a more severe rise in pre-stenotic arterial blood pressure in Fhl2^-/- compared to wildtype mice. The trans-stenotic pressure gradient, however, was identical in both groups. Surprisingly cardiac hypertrophy was less distinct in Fhl2^-/- mice. Left ventricular function was conserved in Fhl2^-/- mice. Vascular contraction measurements proved that aortic rings of Fhl2^-/- mice featured combined contractile dysfunction and disturbed relaxation that was independent of receptor mediation. As a consequence, renal renin-mRNA-expression was suppressed in Fhl2^-/- mice. Angiotensin application, however, induced a severe deterioration of cardiac function in Fhl2^-/- mice combined with exacerbated cardiac hypertrophy.

Fhl2 deficiency encompasses cardiac protection against chronic increases in cardiac afterload due to a suppression of the renin angiotensin axis.