Nanomaterials induce oxidized low-density lipoprotein cellular uptake in macrophages and platelet aggregation

Abstract

Background: Nanomaterials have numerous potential benefits for society, but the potential hazards of nanomaterials on human health are poorly understood. Nanomaterials are known to pass into the circulatory system in humans, causing vascular injuries that might play a role in the development of atherosclerosis. The present study aimed to determine the effects of chronic exposure to nanomaterials on macrophage phenotype and platelet aggregation. Methods and Results: Cultured macrophages (RAW264.7) were treated with carbon black (CB) and water-soluble fullerene (Ceo(OH)24) from 7 to 50 days. Individually, CB had no significant effects on RAW264.7 cell growth, whereas C60(OH)24 alone or CB and C60(OH)24 together with oxidized low-density lipoprotein (Ox-LDL) (100 μg/ml) induced cytotoxic morphological changes, such as Ox-LDL uptake-induced foam cell-like formation and decreased cell growth, in a dose-dependent manner. C60(OH)24 induced LOX-1 protein expression, pro-matrix metalloprotease-9 protein secretion, and tissue factor mRNA expression in lipid-laden macrophages. Although CB or C60(OH)24 alone did not induce platelet aggregation, C60(OH)24 facilitated adenosine diphosphate (ADP)-induced platelet aggregation. Furthermore, C60(OH)24 acted as a competitive inhibitor of ADP receptor antagonists in ADP-mediated platelet aggregation. Conclusions: The present study confirmed novel effects of nanomaterials in macrophages and platelets. These effects suggest that exposure to nanomaterials might be a risk for atherothrombotic diseases.