Galectin‐3, a Biomarker Linking Oxidative Stress and Inflammation With the Clinical Outcomes of Patients With Atherothrombosis

Abstract

BackgroundGalectin‐3 (Gal‐3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal‐3 in cardiovascular (CV) diseases. The role of Gal‐3 as a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown.Methods and ResultsBecause Gal‐3 is involved in monocyte‐to‐macrophage transition, we used fresh isolated monocytes and the in vitro model of macrophage differentiation of THP‐1 cells stimulated with phorbol myristate acetate (PMA). Gal‐3 release is increased by PMA in human monocytes and macrophages, a process involving exosomes and regulated by reactive oxygen species/NADPH oxidase activity. In asymptomatic subjects (n=199), Gal‐3 plasma levels are correlated with NADPH oxidase activity in peripheral blood mononuclear cells (r=0.476; P<0.001) and carotid intima‐media thickness (r=0.438; P<0.001), a surrogate marker of atherosclerosis. Accordingly, Gal‐3 plasma concentrations are increased in patients with carotid atherosclerosis (n=158), compared to control subjects (n=115; 14.3 [10.7 to 16.9] vs. 10.4 [8.6 to 12.5] ng/mL; P<0.001). Finally, on a 5‐year follow‐up study in patients with peripheral artery disease, Gal‐3 concentrations are significantly and independently associated with an increased risk for CV mortality (hazard ratio=2.24, 95% confidence interval: 1.06 to 4.73, P<0.05).ConclusionsGal‐3 extracellular levels could reflect key underlying mechanisms involved in atherosclerosis etiology, development, and plaque rupture, such as inflammation, infiltration of circulating cells and oxidative stress. Moreover, circulating Gal‐3 concentrations are associated with clinical outcomes in patients with atherothrombosis.

Galectin-3 Predicts Long-Term Cardiovascular Death in High-Risk Patients With Coronary Artery Disease

“…23 Gal-3 was shown to predict all-cause and cardiovascular death, and incident heart failure also in healthy subjects, 19,24,25 in patients with peripheral artery disease, 17 and in those with acute coronary syndrome. In the latter, it also predicted hospitalizations for heart failure, 14 reinfarction, 15 heart failure, and cardiovascular mortality.…”

Galectin-3 in acute coronary syndrome

“…Due to the above-mentioned mechanisms, Gal-3 has been proposed as a biomarker for progression and destabilization of atherosclerotic plaques [31,32].…”

“…Firstly, the most common finding among such investigations is that circulating Gal-3 levels are elevated in ACS/AMI, being released during the acute phase of AMI [31,[33][34][35][36][37][38][39]. Indeed, Gal-3 could be part of a survival mechanism of the injured myocardium to cope with the ischemic insult [14].…”

Not all extracellular vesicles were created equal: clinical implications

“…Inflammasome-induced activation of an intracellular caspase-1/calpain cysteine protease cascade facilitates the formation and release of phosphatidylserinepositive, highly procoagulant microparticles (10). Thus, galectin-3, a molecule contributing to atherothrombosis, is released from monocyte macrophages in exosomes (11). Parenchymal cells, such as kidney tubular cells, also release exosomes constitutively (12).…”