Human vasculature-on-a-chip with macrophage-mediated endothelial activation: The biological effect of aerosol from heated tobacco products on monocyte adhesion

• Published in: Toxicology in vitro Vol. 89; p. 105582
• Main Authors: Ohashi, Kazuhiro, Hayashida, Ayaka, Nozawa, Atsuko, Matsumura, Kazushi, Ito, Shigeaki
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2023
• Subjects: Aerosols; Atherosclerosis; Cardiovascular disease; Cytokines - pharmacology; Electronic Nicotine Delivery Systems; Heated tobacco product; Humans; Macrophage; Macrophages; Microphysiological Systems; Monocyte adhesion; Monocytes; Nicotiana; Organ-on-a-chip; Tobacco Products - toxicity; NP; OoC; ISO; HTP; MRTP; Cardiovascular disease; Organ-on-a-chip; ACM; HPHCs; VC; CS; CVD; TPM; SE; PC; Heated tobacco product; Atherosclerosis; Monocyte adhesion; DT3.0a; THP; THS; Macrophage
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2023.105582

Heated tobacco products (HTPs) are expected to have the potential to reduce risks of smoking-associated cardiovascular disease (CVD). However, mechanism-based investigations of the effect of HTPs on atherosclerosis remain insufficient and further studies under human-relevant situations are desired for deeper understanding of the reduced risk potential of HTPs. In this study, we first developed an in vitro model of monocyte adhesion by considering macrophage-derived proinflammatory cytokine-mediated endothelial activation using an organ-on-a-chip (OoC), which provided great opportunities to mimic major aspects of human physiology. Then biological activities of aerosol from three different types of HTPs in terms of monocyte adhesion were compared with that of cigarette smoke (CS). Our model showed that the effective concentration ranges of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were close to the actual condition in CVD pathogenesis. The model also showed that monocyte adhesion was less induced by each HTP aerosol than CS, which may be caused by less proinflammatory cytokine secretion. In summary, our vasculature-on-a-chip model assessed the difference in biological effects between cigarettes and HTPs, and suggested a reduced risk potential of HTPs for atherosclerosis. •In vitro model of monocyte adhesion was developed using OoC.•Inflammatory cytokine-mediated endothelial activation by macrophages was reflected.•Effective doses of TNF-α and IL-1β were close to CVD pathogenesis.•Monocyte adhesion was less induced by HTPs than by cigarette.