New LFA-1 inhibitor Orientin reduces angiotensin II-induced vascular remodeling

Abstract

Background

The interaction between monocytes and vascular endothelium often leads to inflammatory reactions and vascular remodeling. The lymphocyte function-associated antigen 1 (LFA1) plays a crucial role in promoting leukocyte adhesion and migration during inflammatory diseases. However, the role of LFA1 in angiotensin II (Ang II)-induced hypertension and vascular remodeling is not clear. Orientin (Ori) has antioxidant, anti-inflammatory, anticancer, and resistance to myocardial remodeling. However, the role of Orientin remains unclear in angiotensin II (Ang II)-induced hypertension and vascular remodeling.

Methods

In this study, Ang II was used to induce hypertension in mice. We employed various techniques including blood pressure monitoring, pathological staining, Immunofluorescent and Immunohistochemical staining, real time-PCR, vasodilation analysis and other methods to study whether LFA1 antibody and Orientin can regulate vascular remoding.

Results

Our results showed that LFA1 significantly improved Ang II-induced hypertension, inflammation, fibrosis, and oxidative stress. Furthermore, in vitro experiments have substantiated that the use of neutralizing antibodies targeting LFA1 can effectively hinder the migration of macrophages to endothelial cells, which is triggered by Ang II. Additionally, the antibodies also reduce the extent of DNA damage and oxidative stress. Orientin can interact with LFA-1. Then, it was proved by pathological staining that Orientin can inhibit Ang II-induced vascular remodeling.

Conclusion

Here, we identified Orientin as a small molecule inhibitor of LFA-1 with anti-vascular remodeling function. These findings not only suggest that Orientin is a promising compound for the clinical treatment of vascular injury and hypertension, but also provide strategies for the treatment of cardiovascular diseases.