The absence of toll-like receptor (TLR4) signalling has been shown to act cardioprotective in case of ischemia-reperfusion injury and it is also known to influence the development of cardiac hypertrophy. In addition, cardiac hypertrophy does display gender dependent differences. The function of the hypertrophied heart is not only determined by the left ventricular weight but also by a variety of signalling pathways, which are still not fully elucidated. Aim of this study is to describe cardiac function after induction of hypertrophy in male and female mice with normal (C3H/HeN = wildtype, WT) or impaired TLR4-signalling (C3H/HeJ). WT and C3H/HeJ underwent transverse aortic constriction (TAC) and were investigated 2 or 14 days after surgery. Tibia length (TL) was measured and left ventricular weight (LVW), lung weight (LW), and body weight were determined. Haemodynamic parameters like peripheral blood pressure and intra ventricular pressure were recorded in mild anaesthesia by a catheter.

Intact female WT mice have smaller LVW/TL ratios than their male counterparts. Two days following TAC neither LVW/TL nor LW/TL ratios had risen in any of the groups, but peripheral as well as intra ventricular systolic pressure were elevated in all groups. However, intra ventricular diastolic pressure remained normotensive. 14 days following TAC LVW/TL as well as LW/TL ratio had increased in all groups. In female WT mice relative increase in LVW/TL ratio was higher than in WT males leading to similar LVW/TL ratios in both genders. Systolic intra ventricular pressure did not differ among WT mice 14 days after TAC. Intra ventricular diastolic pressure, however, was significantly higher in WT-males, this was also mirrored in their relatively high LW. Thus male WT mice develop diastolic dysfunction after TAC earlier than their female littermates.

In C3H/HeJ mice of both genders the hypertrophic response 14 days following TAC was significantly reduced compared to their WT littermates. Systolic intra ventricular pressure, however, was on the same high level in C3H/HeJ as in WT mice. In contrast diastolic left ventricular pressure was not significantly elevated in C3H/HeJ mice independently of sex. LW of C3H/HeJ was also not increased after 14 days of TAC reflecting the preserved diastolic function in these animals. Absence of TLR4 signalling seems to mitigate TAC induced hypertrophy independently of sex. Reduced hypertrophy is accompanied by a conserved diastolic function in male C3H/HeJ mice. TLR4 signalling seems to be an important prohypertrophic pathway. The detailed inflammatory cascades have to be further investigated.