(Nano)particle exposure, acute phase response and cardiovascular disease

抄録

Particle inhalation has been causally linked to diseases including cancer, COPD, fibrosis and cardiovascular disease. We have proposed a biological mechanism of action for particle-induced cardiovascular disease causally linking particle exposure to induction of acute phase response, which is a known risk factor for atherosclerosis and cardiovascular disease.

Inhalation and pulmonary deposition of particles induces inflammation, which is proportional to the total surface area of the pulmonary-deposited particles. In mice, inflammation is accompanied by an acute phase response, which is long-lasting for insoluble particles. Acute phase protein Serum Amyloid A (SAA) is among the most differentially expressed genes in lung tissue following particle exposure.

SAA is causally implicated in atherosclerosis and both overexpression and pulmonary dosing of SAA promotes plaque formation in ApoE-/- mice. In humans, controlled exposure to metal oxides and combustion particles induce dose-dependent increases in blood levels of SAA and C-reactive protein. Blood levels of acute phase proteins SAA and C-reactive protein are risk factors for cardiovascular disease in prospective, epidemiological studies.

Nanoparticles have a higher specific surface area than larger particles with similar chemical composition, and therefore, nanoparticles are more hazardous than larger particles of similar chemical composition in relation to cardiovascular disease. This underscores cardiovascular disease as a particle-induced occupational disease.