Tlr2 deficiency does not limit the development of left ventricular hypertrophy in a model of transverse aortic constriction induced pressure overload

Abstract

BackgroundToll-like receptors (TLRs) are involved in a variety of cardiovascular disorders, including septic cardiomyopathy, ischemia/reperfusion, heart failure, and cardiac hypertrophy. Previous research revealed that TLR4 promotes cardiac hypertrophy in vivo. Therefore, we investigated whether TLR2 is also involved in the development of cardiac hypertrophy.MethodsTlr2 deficient and wild type mice were subjected to transverse aortic constriction (TAC) or sham operation procedure. Left ventricular, heart and lung weights as well as hemodynamic parameters were determined after 3, 14 or 28 days. Real-time RT PCR was used to evaluate left ventricular gene expression. Protein content was determined via ELISA.ResultsTAC increased systolic left ventricular pressure, contraction and relaxations velocities as well as the heart weight in both genotypes. Tlr2 deficiency significantly enhanced cardiac hypertrophy after 14 and 28 days of TAC. Left ventricular end-diastolic pressure and heart rate increased in Tlr2−/− TAC mice only. Fourteen days of TAC led to a significant elevation of ANP, BNP, TGFβ and TLR4 mRNA levels in Tlr2−/− left ventricular tissue.ConclusionThese data suggest that Tlr2 deficiency may promote the development of cardiac hypertrophy and ventricular remodeling after transverse aortic constriction.

Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload

“…showed a lower heart weight in TLR2 −/− mice measured at 14 days and 28 days after TAC 12 . In contrast, another study found a higher heart weight in TLR2 −/− mice compared to WT at 14 and 28 days but no difference was detected in left ventricle weight between WT and TLR2 −/− mice 13 . We found in this study that hypertrophy, as evidenced by the increase in LV weight and mRNA levels of two hypertrophic markers ANP and BNP, occurred in both WT and TLR2 −/− mice to a similar extent from week 1 up to week 8 in response to sustained pressure overload (Fig.…”

“…We and Bualeong et al . 13 achieved more severe aortic constriction using a 27 gauge needle, and both studies did not find a difference in left ventricular weight suggesting that the role of TLR2 probably depends on the severity of pressure overload. Furthermore, both studies found that lung weight after TAC did not differ between TLR2 −/− and WT mice.…”

“…Furthermore, both studies found that lung weight after TAC did not differ between TLR2 −/− and WT mice. Besides clear differences in procedure, the role of the mouse origin is unclear 13 and in all these studies mice are on a C57BL/6 background.…”

“…In contrast, angiotensin-induced LV hypertrophy was similar between TLR2 −/− and WT at 7 days, but TLR2 deficiency in bone marrow-derived cells reduced fibrosis and inflammation 11 . Data in transverse aortic constriction (TAC) models are conflicting: TLR2 deficiency exacerbated cardiac dysfunction in spite of reduced hypertrophy and fibrosis at 14 and 28 days in one study 12 ; while in another study, TLR2 deficiency increased LV hypertrophy at the same time points 13 .…”

Toll-like receptor 2 deficiency hyperactivates the FoxO1 transcription factor and induces aging-associated cardiac dysfunction in mice

“…On similar lines, TLR2 deficiency reduces the severity of atherosclerosis in low-density lipoprotein receptordeficient mice (20). Contrast to these studies suggesting a detrimental role for TLR2 signalling in heart, few recent reports suggest that TLR2 deficiency exacerbates cardiac hypertrophy and remodelling after transverse aortic constriction in mice (12,21). Notably, TLR2 deficiency causes mature-onset obesity in mice and increases the susceptibility to high-fat dietinduced weight gain.…”