Effect of Toll-like Receptor 4 on Cardiac Hypertrophy in Hypertension

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We investigated the role of Toll-like receptor 4 (TLR4) in cardiac hypertrophy and function following angiotensin II (Ang II) or norepinephrine (NE) -induced pressure overload in mice in vivo.TLR4-knocked out mice, and wild-type (WT) genetic background mice (BALB/c) were randomized into two groups and implanted osmotic minipumps of Angiotensin II (AT II) or Norepinephrine (NE) for 2 weeks. Both Ang II and NE induced a significant increase in systolic blood pressures among the four groups (p<0.05), while blood pressures and heart rates were not significantly different among the four groups throughout the experiments. Compared with Ang II -induced pressure overload WT mice, Ang II-induced pressure overload TLR4-knockout mice showed a significant increase in both ejection fraction (EF) and % fractional shortening (%FS) (p<0.05), and also demonstrated a smaller left ventricular end-systolic dimension (LVESd, p<0.05). In contrast, compared with NE-induced pressure overload WT mice, NE-induced pressure overload TLR4-knockout mice showed smaller LVESd and an increase in EF and %FS; these indices, however, did not reach statistical significance. Left ventricular end-diastolic dimension, interventricular septum, left ventricular diastolic wall thickness, and heart weight did not differ among the four groups. Compared with Ang II-induced pressure overload WT mice, Ang II-induced pressure overload TLR4-knockout mice showed a significant increase in both perivascular collagen volume fraction (p<0.05), and wall-to-lumen ratio (p<0.05). These results suggest that TLR4 may be involved in the development of Ang II-induced cardiac systolic dysfunction without affecting cardiac hypertrophy.