Integrin CD11b Contributes to Hypertension and Vascular Dysfunction Through Mediating Macrophage Adhesion and...

Area of Science:

• Immunology
• Cardiovascular Biology
• Cell Biology

Background:

• Leukocyte adhesion to endothelium, an early inflammatory response, is primarily regulated by β2-integrins.
• The specific role of integrin CD11b/CD18 in hypertension pathogenesis and vascular dysfunction remains largely undetermined.

Purpose of the Study:

• To investigate the role of integrin CD11b/CD18 in the development of hypertension and associated vascular dysfunction.
• To explore the therapeutic potential of targeting CD11b in managing hypertension.

Main Methods:

• Established hypertension in mice using angiotensin II or deoxycorticosterone acetate salt.
• Utilized CD11b-deficient mice, bone marrow transplantation, and anti-CD11b neutralizing antibodies or agonists.
• Assessed blood pressure, inflammatory cell infiltration, aortic remodeling, vascular function, and cell adhesion/migration in vitro.
• Analyzed the correlation between circulating CD11b+ immune cells and hypertension in human patients.

Main Results:

• CD11b and CD18 expression, along with CD45+CD11b+CD18+ myeloid cells, were significantly elevated in the aortas of angiotensin II-infused mice.
• CD11b ablation or inhibition markedly reduced hypertension, aortic remodeling, superoxide generation, and vascular dysfunction by decreasing macrophage infiltration, adhesion, and migration.
• Administration of a CD11b agonist exacerbated angiotensin II-induced hypertension.
• Elevated levels of circulating CD45+CD11b+CD18+ myeloid cells were observed in hypertensive patients compared to normotensive controls.

Conclusions:

• CD11b-expressing myeloid cells are critically involved in the pathogenesis of hypertension and vascular dysfunction.
• Targeting CD11b presents a promising novel therapeutic avenue for the treatment of hypertension.