Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis

Abstract

Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of Gal-3 in 76 patients with AAA (AAA group) and 97 controls (CTL group) as well as in angiotensin II (Ang-II)-infused ApoE knockout mice. Additionally, conditioned media (CM) were used to polarize THP-1 monocyte to M1 macrophages with or without Gal-3 inhibition through small interfering RNA targeted deletion to investigate whether Gal-3 inhibition could attenuate macrophage-induced inflammation and smooth muscle cell (SMC) apoptosis. Our results showed a markedly increased expression of Gal-3 in the plasma and aorta in the AAA patients and experimental mice compared with the CTL group. An in vitro study demonstrated that the M1 cells exhibited increased Gal-3 expression. Gal-3 inhibition markedly decreased the quantity of macrophage-induced inflammatory regulators, including IL-8, TNF-α, and IL-1β, as well as messenger RNA expression and MMP-9 activity. Moreover, Gal-3-deficient CM weakened SMC apoptosis through Fas activation. These findings prove that Gal-3 may contribute to AAA progression by the activation of inflammatory macrophages, thereby promoting SMC apoptosis.

Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes

“…In patients with altered renal function, increased plasma levels of galectin-3 have been associated with higher risk of renal function decline, incident chronic kidney disease, and renal failure [ 52 ]. Galectin-3 is involved in many processes during acute inflammatory responses, including neutrophil activation and adhesion and chemoattraction of macrophages [ 56 , 57 ]. Lu HY et al demonstrated that galectin-3 is responsible for macrophage activation by inducing monocyte-macrophage differentiation and amplifying inflammation [ 56 ].…”

“…Galectin-3 is involved in many processes during acute inflammatory responses, including neutrophil activation and adhesion and chemoattraction of macrophages [ 56 , 57 ]. Lu HY et al demonstrated that galectin-3 is responsible for macrophage activation by inducing monocyte-macrophage differentiation and amplifying inflammation [ 56 ]. Moreover, several studies have postulated that macrophages are the major source of galectin-3 driving renal fibrosis through myofibroblast activation [ 58 , 59 ].…”

MIF Regulates M1 Macrophage Polarization via CD74/CXCR2/JNK Pathway and Mediates Aortic Dissection in Mice

“…46,47 The activated inflammatory macrophages may up-regulate the expression of Fas protein in VSMC via TNF-α and IL-1β, promote VSMC apoptosis, and the proliferation ability of VSMC was also influenced by macrophages, which regulated the formation of intima. 48,49 Through single cell sequencing, it was found that the receptor-ligand interaction between VSMC and immune cell population in aortic dissection was significantly up-regulated, especially for macrophages and T cells. Therefore, compared with single cells such as macrophages or VSMCs, the interaction between two or even more types of cells played a more significant role in the process of vascular remodeling in aortic dissection.…”

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target

“…There exist two activated states of macrophages, characterized by a pro-inflammatory classical activation phenotype (M1) and an anti-inflammatory alternative activation phenotype (M2) [82]. Blocking the expression of Gal3 reduced the expression of IL-8, TNF-α, and IL-1β in M1 macrophages [83]. Moreover, Gal3 takes part in the polarization of the M2 subtype, while M2 macrophages could upregulate the secretion of Gal3 in return.…”