Blockade of intercellular adhesion molecule-1 prevents angiotensin II-induced hypertension and vascular dysfunction

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Abstract

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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References

  1. 1.

    Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003;139:761–76.

  2. 2.

    Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep. 2010;12:448–55.

  3. 3.

    Wang L, Zhao XC, Cui W, Ma YQ, Ren HL, Zhou X, et al. Genetic and pharmacologic inhibition of the chemokine receptor CXCR2 prevents experimental hypertension and vascular dysfunction. Circulation. 2016;134:1353–68.

  4. 4.

    Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011;124:1370–81.

  5. 5.

    Schiffrin EL, Touyz RM. From bedside to bench to bedside: role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension. Am J Physiol Heart Circ Physiol. 2004;287:H435–446.

  6. 6.

    Hussain M, Awan FR. Hypertension regulating angiotensin peptides in the pathobiology of cardiovascular disease. Clin Exp Hypertens. 2018;40:344–52.

  7. 7.

    Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996;84:345–57.

  8. 8.

    Aricescu AR, Jones EY. Immunoglobulin superfamily cell adhesion molecules: zippers and signals. Curr Opin Cell Biol. 2007;19:543–50.

  9. 9.

    Anbarasan C, Bavanilatha M, Latchumanadhas K, Ajit Mullasari S. ICAM-1 molecular mechanism and genome wide SNP’s association studies. Indian Heart J. 2015;67:282–7.

  10. 10.

    Pastore L, Tessitore A, Martinotti S, Toniato E, Alesse E, Bravi MC, et al. Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo. Circulation. 1999;100:1646–52.

  11. 11.

    Kuwahara F, Kai H, Tokuda K, Niiyama H, Tahara N, Kusaba K, et al. Roles of intercellular adhesion molecule-1 in hypertensive cardiac remodeling. Hypertension. 2003;41(3 Pt 2):819–23.

  12. 12.

    Li N, Yang H, Wang M, Lü S, Zhang Y, Long M. Ligand-specific binding forces of LFA-1 and Mac-1 in neutrophil adhesion and crawling. Mol Biol Cell. 2018;29:408–18.

  13. 13.

    Tsakadze NL, Sen U, Zhao Z, Sithu SD, English WR, D’Souza SE. Signals mediating cleavage of intercellular adhesion molecule-1. Am J Physiol Cell Physiol. 2004;287:C55–63.

  14. 14.

    Komatsu S, Panes J, Russell JM, Anderson DC, Muzykantov VR, Miyasaka M, et al. Effects of chronic arterial hypertension on constitutive and induced intercellular adhesion molecule-1 expression in vivo. Hypertension. 1997;29:683–9.

  15. 15.

    Lee JR, Han JJ, Seo JW. Correlation between ICAM-1 and functional recovery of piglet myocardium with leukocyte-depleted reperfusion. Ann Thorac Surg. 2000;70:1531–5.

  16. 16.

    Cheng QL, Chen XM, Li F, Lin HL, Ye YZ, Fu B. Effects of ICAM-1 antisense oligonucleotide on the tubulointerstitium in mice with unilateral ureteral obstruction. Kidney Int. 2000;57:183–90.

  17. 17.

    Wang L, Zhang YL, Lin QY, Liu Y, Guan XM, Ma XL, et al. CXCL1-CXCR2 axis mediates angiotensin II-induced cardiac hypertrophy and remodelling through regulation of monocyte infiltration. Eur Heart J. 2018;39:1818–31.

  18. 18.

    Wang X, Wang HX, Li YL, Zhang CC, Zhou CY, Wang L, et al. MicroRNA Let-7i negatively regulates cardiac inflammation and fibrosis. Hypertension. 2015;66:776–85.

  19. 19.

    Liao YH, Xia N, Zhou SF, Tang TT, Yan XX, Lv BJ, et al. Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration. J Am Coll Cardiol. 2012;59:420–9.

  20. 20.

    Takamatsu S. Naturally occurring cell adhesion inhibitors. J Nat Med. 2018;72:817–35.

  21. 21.

    Trott DW, Harrison DG. The immune system in hypertension. Adv Physiol Educ. 2014;38:20–24.

  22. 22.

    Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132–40.

  23. 23.

    Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol. 2009;27:165–97.

  24. 24.

    Nabah YN, Mateo T, Cerda-Nicolas M, Alvarez A, Martinez M, Issekutz AC, et al. L-NAME induces direct arteriolar leukocyte adhesion, which is mainly mediated by angiotensin-II. Microcirculation. 2005;12:443–53.

  25. 25.

    Bowes MO, Zivin JA, Rothlein R. Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp Neurol. 1993;119:215–9.

  26. 26.

    Lindsberg PJ, Carpen O, Paetau A, Karjalainen-Lindsberg ML, Kaste M. Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation. 1996;94:939–45.

  27. 27.

    DeSouza CA, Dengel DR, Macko RF, Cox K, Seals DR. Elevated levels of circulating cell adhesion molecules in uncomplicated essential hypertension. Am J Hypertens. 1997;10(12Pt1):1335–41.

  28. 28.

    Yasukawa H, Imaizumi T, Matsuoka H, Nakashima A, Morimatsu M. Inhibition of intimal hyperplasia after balloon injury by antibodies to intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1. Circulation. 1997;95:1515–22.

  29. 29.

    Nishikawa K, Guo YJ, Miyasaka M, Tamatani T, Collins AB, Sy MS, et al. Antibodies to intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis. J Exp Med. 1993;177:667–77.

  30. 30.

    Huo Y, Ley K. Adhesion molecules and atherogenesis. Acta Physiol Scand. 2001;173:35–43.

  31. 31.

    Mosig S, Rennert K, Krause S, Kzhyshkowska J, Neunübel K, Heller R, et al. Different functions of monocyte subsets in familial hypercholesterolemia: potential function of CD14+ CD16+ monocytes in detoxification of oxidized LDL. FASEB J. 2009;23:866–74.

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Acknowledgements

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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Correspondence to Qiu-Yue Lin or Hui-Hua Li.

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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

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