Colchicine exerts anti‐atherosclerotic and ‑plaque‐stabilizing effects targeting foam cell formation

Abstract

Colchicine is a broad-acting anti-inflammatory agent that has attracted interest for repurposing in atherosclerotic cardiovascular disease. Here, we studied its ability at a human equivalent dose of 0.5 mg/day to modify plaque formation and composition in murine atherosclerosis and investigated its actions on macrophage responses to atherogenic stimuli in vitro. In atherosclerosis induced by high-cholesterol diet, Apoe −/− mice treated with colchicine had 50% reduction in aortic oil Red O + plaque area compared to saline control (p = .001) and lower oil Red O + staining of aortic sinus lesions (p = .03). In vitro, addition of 10 nM colchicine inhibited foam cell formation from murine and human macrophages after treatment with oxidized LDL (ox-LDL). Mechanistically, colchicine downregulated glycosylation and surface expression of the ox-LDL uptake receptor, CD36, and reduced CD36 + staining in aortic sinus plaques. It also decreased macrophage uptake of cholesterol crystals, resulting in lower intracellular lysosomal activity, inhibition of the NLRP3 inflammasome, and reduced secretion of

Cluster of Differentiation-44-Targeting Prussian Blue Nanoparticles Onloaded with Colchicine for Atherosclerotic Plaque Regression in a Mice Model

“…However, the oil red O staining demonstrated no significant change in lipid contents within plaque after treatment of colchicine or col@PBNP@HA. Previous studies have suggested that inflammation and foam cell formation share many similar pathways and that colchicine can inhibit foam cell formation. ,− Nevertheless, the results of the present research indicated that col@PBNP@HA had no effect on foam cell formation, which may be attributed to the discrepancy in the administration period.…”

“…It is necessary to verify the good in vivo biocompatibility and low organ toxicity of col@PBNP@HA. In this study, we applied the nanoparticles at a colchicine dose of 0.1 mg/kg according to previous reports . Histomorphological analysis of the tissue of hearts, livers, spleens, lungs, and kidneys 7 d after single injection showed no organ impairment, including necrosis, hemorrhage, and inflammatory cell infiltration (Figure A).…”

“…In this study, we applied the nanoparticles at a colchicine dose of 0.1 mg/kg according to previous reports. 38 Histomorphological analysis of the tissue of hearts, livers, spleens, lungs, and kidneys 7 d after single injection showed no organ impairment, including necrosis, hemorrhage, and inflammatory cell infiltration (Figure 4A). Besides, sera results showed no damage of col@PBNP@HA on liver, kidney, and heart (Figure 4B).…”

Inflammasomes in Atherosclerosis—From Pathophysiology to Treatment

“…Colchicine, an important anti-inflammatory molecule that has been effective in the prevention of major adverse cardiovascular events, has been suggested as an NLRP3 inflammasome inhibitor. Preclinically, the administration of colchicine in murine and human macrophages treated with oxidized LDL resulted in the inhibition of NLRP3 inflammasome formation [ 57 ]. Moving to clinical studies, Robertson et al had initially proven that the administration of colchicine in patients with ACS resulted in lower expression of NLRP3 inflammasome markers (IL-1β, IL-18, pro-caspase-1, and caspase-1) from peripheral venous blood monocytes [ 58 ].…”

Colchicine protects against the development of experimental abdominal aortic aneurysm

“…Studies showed that colchicine treatment could reduce the risk of cardiovascular events including myocardial infarction, chronic coronary disease, recurrent pericarditis and atrial fibrillation [ 10 , 12 , 15–17 ]. Recently, it was found that colchicine exerted anti-atherosclerotic and plaque-stabilizing effects by inhibition of foam cell formation and inflammation in murine atherosclerosis [ 18 ], and more recently (in June 2023), low-dose colchicine (0.5 mg/d orally) was approved to reduce the risk of cardiovascular events in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease by the U.S. Food and Drug Administration [ 19 ].…”