Objective:
Hypertension is associated with a low-grade systemic
inflammation in cardiovascular system. Macrophage infiltration may initiate an inflammatory process that contributes to vascular and
ventricular remodeling in hypertensive human and mice. The present study investigated the effect of chemical depletion of macrophage using
liposome encapsulated
clodronate (LEC) on
cardiac hypertrophy and remodeling in
angiotensin (Ang) II hypertensive mice.Methods: C57BL/6 mice received an Ang II (1.1 mg/kg/day with a minipump) infusion for 2 weeks to induce
hypertension. Endothelium-dependent relaxation (ED) was examined by organ bath,
hematoxylin and staining and Masson-Trichrome staining were used to evaluate aorta and
cardiac hypertrophy and
fibrosis.Results: Ang II infusion significantly increased systolic blood pressure (SBP),
cardiac hypertrophy and
fibrosis, and impaired EDR accompanied by increased macrophage infiltration in the heart. Treatment with LEC significantly lowered Ang II-induced
cardiac hypertrophy and
fibrosis and cardiac macrophage infiltration, and improved EDR with a mild reduction in SBP. Ang II increased the expression of inflammatory
cytokines tumor necross factor alpha and
interleukin 1 beta and profibrotic
factors transforming growth factor beta 1 and
fibronectin in the heart, with was reduced by LEC treatment. Treatment with LEC prevented Ang II-induced the phosphorphorylation of ERK1/2 and
c-Jun-N-terminal kinase.Conclusions: Our study suggests that cardiac macrophage may be critical for hypertensive
cardiac hypertrophy and remodeling, the underlying mechanisms may involve initial heart
inflammation and the activation of hypertrophic MAPKs pathway.