Mechanism of Inhibition of M1 Macrophage Expression and Activation of MIP-1α/CCL3 Signaling Pathway on Vascular Remodeling

Abstract

Macrophages mediate the activation of MIP-1α/CCL3 signaling and participate in inflammatory response. In our study, M1 gene-deficient mice were used to assess the effect and mechanism of specific inhibition of macrophage M1 expression on angiotensin II-induced hypertensive vascular remodeling. Fifty 8-week-old male Lyz2-cre M1 gene-deficient mice and 50 Cre mice were divided into control group (saline group) and experimental group (angiotensin II group) followed by HE staining, collagen or elastin staining as well as measuring wall thickness. DHE staining was performed to observe the density of coronary artery and aortic oxidative stress. PCR Array was used to detect cytokine changes which were then verified by RT-PCR. The changes of aortic inflammatory factors were assessed by immunofluorescence and Western blotting. IHC was to measure MIP-1α level. Specific inhibition of M1 expression aggravated AngII-induced hypertensive vascular remodeling; Ang II stimulation increased vascular superoxide production by aggravation of ROS; specific inhibition of macrophage M1 expression significantly up-regulated vascular inflammatory cytokines and the expression and activation of MIP-1α/CCL3 in vascular smooth muscle cells to aggravate vascular remodeling. Further, in vitro cell experiments showed that MIP-1α significantly up-regulated CD31 tube staining. M1 is involved in AngII-induced hypertensive vascular remodeling by mediating the release of macrophage inflammatory factor MIP-1α/CCL3.