Abstract 338: 90K Inhibits Human Macrophage Foam Cell Formation and Is Associated with Reduced Plaque Burden and Reduced Adverse Cardiovascular Events in Patients with Coronary Artery Disease
Objective: 90K (also known as galectin-3 binding protein) is a secreted protein that modulates inflammation in vivo. We hypothesized that 90K may affect atherosclerosis through its effects on macrophages.
Methods and results: In human primary macrophages, recombinant human 90K reduced gene and protein expression of the scavenger receptors CD36 and SR-A in a dose- and time-dependent manner. Accordingly, uptake of DiI-labeled acetylated (acLDL) or oxidized low density lipoprotein (oxLDL) was significantly reduced after pre-treatment with 90K. Oil red O staining confirmed 90K-dependent reduction of foam cell formation induced by oxLDL after 24 hours. 90K expression in macrophage-rich areas of human atherosclerotic plaques was confirmed by immunohistochemistry in post mortem coronary arteries. In 122 patients undergoing coronary angiography 90K plasma levels were measured by ELISA. Hereby, there was no significant difference between patients with (n=89) and without (n=33) coronary artery disease (CAD). However, 90K plasma levels were significantly lower in CAD patients with at least one coronary artery stenosis ≥50% (n=37) compared to those with lumen narrowing <50% (n=52, P=0.044). By measuring total coronary artery plaque volume by cardiac computed tomography angiography (CCTA) in 56 of these patients with angiographically confirmed CAD, we found an inverse correlation between plaque volume and 90K plasma levels (r=-0.318, P=0.018). This correlation remained significant after multivariate analysis taking into account established cardiovascular risk factors including high sensitivity C reactive protein. In an independent cohort of 77 patients with angiographically confirmed CAD, low 90K plasma levels were associated with increased incidence of adverse cardiovascular events (as defined by cardiovascular death, myocardial infarction, or stroke) within one year (P=0.007). Again, this correlation remained significant in a multivariate Cox proportional hazards regression analysis (P=0.039, hazard ratio 0.230, 95%-CI 0.097-0.935).
Conclusions: We propose a protective role of 90K in coronary artery disease. By modulating macrophage foam cell formation, 90K may reduce plaque growth and promote plaque stability preventing adverse cardiovascular events.
- © 2012 by American Heart Association, Inc.