Monocyte and adhesion infiltration into the arterial subendothelium are initial steps in hypertension development. The endothelial intercellular adhesion molecule-1 (ICAM-1) has been implicated in the recruitment and adhesion of leukocytes in several cardiac diseases. However, the role of ICAM-1 in angiotensin II (Ang II)-induced hypertension development remains unknown. Hypertension was induced by administering an infusion of Ang II (1000 ng/kg/min) to wild-type (WT) mice treated with an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse/day, respectively). Blood pressure was determined using the tail-cuff system. Vascular remodeling was assessed by performing a histological examination. Inflammation and reactive oxygen species (ROS) levels were determined by using immunostaining. Vascular dysfunction was assessed by aortic ring assay. The expression of fibrotic markers, cytokines and NOX was evaluated by quantitative real-time PCR analysis. Our results demonstrate that Ang II infusion markedly increased the ICAM-1 level in the aorta. Blocking ICAM-1 with a neutralizing antibody significantly attenuated Ang II-induced arterial hypertension, vascular hypertrophy, fibrosis, macrophage infiltration, and ROS production and improved vascular relaxation. In conclusion, ICAM-1-mediated monocyte adhesion and migration play a critical role in Ang II-induced arterial hypertension and vascular dysfunction. ICAM-1 inhibitors may represent a new therapeutic strategy for the treatment of this disease.
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This work was supported by grants from the State Key Program of National Natural Science Foundation of China 81630009 (H.H.L.), Dalian High-Level Talents Innovation and Entrepreneurship Projects 2015R019 (H.H.L.), and the Chang Jiang Scholar Program of China T2011160 (H.H.L.).
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Lang, P., Bai, J., Zhang, Y. et al. Blockade of intercellular adhesion molecule-1 prevents angiotensin II-induced hypertension and vascular dysfunction. Lab Invest (2019) doi:10.1038/s41374-019-0320-z