Galectin-1 in Cardiovascular Pathogenesis: Unraveling Dual Roles and Mechanistic Insights in Emerging Research

Abstract

Galectin-1 (Gal-1), a β-galactoside-binding lectin, plays a complex role in cardiovascular diseases (CVDs), exerting both protective and pathological effects depending on the context. This review synthesizes findings from the past decade to explore Gal-1's involvement in key aspects of CVD pathogenesis, including vascular homeostasis, inflammation regulation, atherosclerosis progression, myocardial remodeling, and heart failure. While Gal-1 supports endothelial integrity and immune modulation, its dysregulation contributes to disease progression through pro-inflammatory signaling, fibrosis, and adverse cardiac remodeling. Emerging evidence suggests that Gal-1 holds potential as both a biomarker for risk assessment and a therapeutic target. However, critical knowledge gaps remain, particularly regarding its context-dependent effects, the limited scope of clinical trials, and unresolved mechanistic insights. Addressing these challenges will be essential to fully harness Gal-1's therapeutic potential in cardiovascular medicine, guiding future research efforts toward precision interventions and clinical applications.

Keywords: cardiovascular diseases; dual role; galectin-1; risk assessment; therapeutic target.

Figure 1

Dual role of galectin-1 in cardiovascular disease pathogenesis. Galectin-1 (Gal-1) plays a complex role in cardiovascular diseases (CVDs), exhibiting both protective and pathological effects depending on the context. On the beneficial side, Gal-1 supports endothelial cell survival, regulates angiogenesis, suppresses inflammation, and modulates immune responses to mitigate vascular damage and myocardial injury. Conversely, Gal-1 can also drive disease progression by fostering vascular inflammation, accelerating atherosclerosis, inducing fibrosis, and exacerbating adverse cardiac remodeling. This figure illustrates the nuanced, context-dependent functions of Gal-1 in CVD pathogenesis, underscoring its potential as both a biomarker for disease progression and a target for therapeutic intervention. In the diagram, “+” denotes beneficial effects, while “−” signifies pathological contributions.

Figure 2

Molecular mechanisms of galectin-1 in cardiovascular diseases. Galectin-1 (Gal-1) exerts its effects in cardiovascular diseases (CVDs) through multiple molecular mechanisms. On the protective side, Gal-1 inhibits pro-inflammatory cytokine release, promotes macrophage polarization toward an anti-inflammatory M2 phenotype, and enhances endothelial cell survival and angiogenesis. These actions contribute to vascular repair, reduced atherosclerotic plaque progression, and improved myocardial recovery post-injury. However, Gal-1 can also facilitate pathological processes, such as enhancing fibroblast activation, increasing extracellular matrix deposition, and promoting cardiac fibrosis, which contribute to adverse ventricular remodeling and heart failure progression. Gal-1 influences calcium channel activity, affecting vascular tone and blood pressure regulation. This figure provides an overview of Gal-1’s molecular interactions with key cellular pathways in the cardiovascular system, emphasizing its complex and context-dependent roles.

Figure 3

Galectin-1 in atherosclerosis progression and plaque stability. Galectin-1 (Gal-1) influences multiple stages of atherosclerosis, exhibiting both protective and pathological effects. In early atherosclerosis, Gal-1 modulates endothelial function by reducing adhesion molecule expression (e.g., VCAM-1, ICAM-1), limiting leukocyte adhesion and infiltration into the vascular wall. It also promotes macrophage polarization toward an anti-inflammatory M2 phenotype, reducing pro-inflammatory cytokines such as IL-6 and TNF-α. These actions contribute to plaque stabilization and reduced atherosclerotic burden. However, under certain conditions, Gal-1 may enhance foam cell formation, promote vascular smooth muscle cell migration, and contribute to plaque progression. Additionally, Gal-1 binds to lipoprotein(a), which may influence lipid metabolism and atherogenesis. This figure illustrates the multifaceted role of Gal-1 in atherosclerosis development, highlighting its potential as a therapeutic target for stabilizing vulnerable plaques and reducing cardiovascular risk.

Figure 4

Galectin-1 in myocardial infarction and heart failure progression. Galectin-1 (Gal-1) plays a dual role in myocardial infarction (MI) and heart failure (HF) by regulating inflammatory responses, fibrosis, and tissue remodeling. After MI, Gal-1 exerts cardioprotective effects by suppressing pro-inflammatory cytokines (e.g., TNF-α, IL-6), reducing cardiomyocyte apoptosis, and promoting angiogenesis to facilitate tissue repair. However, in chronic heart failure, Gal-1 can contribute to pathological cardiac remodeling by stimulating fibroblast activation, increasing extracellular matrix deposition, and promoting myocardial fibrosis, which leads to ventricular stiffening and diastolic dysfunction. Additionally, Gal-1 influences immune cell polarization, affecting macrophage-mediated inflammation and cardiac healing. This figure illustrates the complex and context-dependent actions of Gal-1 in MI and HF, emphasizing its potential as a biomarker and therapeutic target in cardiovascular diseases. In the diagram, “+” denotes beneficial effects, while “−” signifies pathological contributions. The arrow-up indicates an increase, while the arrow-down represents a decrease.