The interplay of galectins-1, -3, and -9 in the immune-inflammatory response underlying cardiovascular and metabolic disease

Abstract

Galectins are β-galactoside-binding proteins that bind and crosslink molecules via their sugar moieties, forming signaling and adhesion networks involved in cellular communication, differentiation, migration, and survival. Galectins are expressed ubiquitously across immune cells, and their function varies with their tissue-specific and subcellular location. Particularly galectin-1, -3, and -9 are highly expressed by inflammatory cells and are involved in the modulation of several innate and adaptive immune responses. Modulation in the expression of these proteins accompany major processes in cardiovascular diseases and metabolic disorders, such as atherosclerosis, thrombosis, obesity, and diabetes, making them attractive therapeutic targets. In this review we consider the broad cellular activities ascribed to galectin-1, -3, and -9, highlighting those linked to the progression of different inflammatory driven pathologies in the context of cardiovascular and metabolic disease, to better understand their mechanism of action and provide new insights into the design of novel therapeutic strategies.

The changing landscape of drug clinical trials on cardiometabolic diseases in China, 2009–2021

“…Epidemiological studies have confirmed that the morbidity of adverse cardiovascular events significantly increased in patients with type 2 diabetes, hyperlipidemia, hypertension, or obesity [ 17 – 21 ]. The core pathological mechanisms of these metabolic disorders are insulin resistance and chronic inflammatory signal activation, which involve a variety of mechanisms and signals and form a complex regulatory network [ 22 – 24 ]. More importantly, these metabolic diseases bring pathological effects to the cardiovascular system directly or indirectly.…”

Gastrointestinal barrier function, immunity, and neurocognition: The role of human milk oligosaccharide (hMO) supplementation in infant formula

“…Specifically, hMOs are able to bind to galectin‐1, ‐2, ‐3 ‐7, ‐8, and ‐9 (Hirabayashi et al., 2002). As these receptors are expressed by immune cells, this interaction causes a direct effect on the immune system in both pro‐ and anti‐inflammatory manners (Mansour et al., 2022). Another type of lectin receptor that hMOs have been found to bind to are sialic acid binding immunoglobulin‐like lectins (Siglecs).…”

Do Serum Galectin-9 Levels in Women with Gestational Diabetes and Healthy Ones Differ before or after Delivery? A Pilot Study

“…The development of T2DM is associated with low-grade inflammation, causing an increased concentration of pro-inflammatory cytokines, which can interfere with the insulin response mechanisms. This causes an increase in insulin production and secretion, and eventually insulin resistance [ 16 ].…”

“…Galectin-9 is a protein expressed mainly in the liver, small intestine, and thymus [ 16 , 24 ]. The half-life of galectin-9 is short, ranging from 30 to 60 min.…”

“…In response to glucose stimulation, GLUT-2 mediates the entry of glucose into the cell by translocating to the plasma membrane. Galectin-9 expression has been shown to increase in subcutaneous adipose tissue and in macrophages of visceral adipose tissue in obese mice, as well as in the serum of patients with T2DM [ 16 ]. In pregnancy, trophoblast cells secrete galectin-9, which can cause Tim-3+ peripheral NK cells to acquire a decidual NK phenotype, defined by high levels of interleukin 4, low levels of tumor necrosis factor α, and reduced cytotoxic capacity.…”