| Summary: | Anti-β2-glycoprotein I antibodies (aβ2GPI) represent a potential pathogenic candidate for coronary artery diseases. High avidity aβ2GPI (HAv aβ2GPI) are known to be associated with thrombotic and obstetric manifestations in patients with antiphospholipid syndrome, who are also susceptible to the development of premature atherosclerosis. However, there is little information about how human coronary artery endothelial cells (HCAEC) are affected by HAv aβ2GPI. The purpose of our study was to evaluate the pathophysiological effects of HAv aβ2GPI on HCAEC and determine their influence on cytokine expression and migration of peripheral blood mononuclear cells. Following the two hit hypothesis, we co-stimulated HAv aβ2GPI-treated HCAEC in the presence and absence of the acute phase protein serum amyloid A (SAA). HAv aβ2GPI induced in vitro HCAEC dysfunction, through the ERK1/2 signaling pathway, promoted the expression of chemokines (MCP-1, GROα and IL-8) and IL-6, which led to the attraction and migration of peripheral blood mononuclear cells. These effects were potentiated and intensified in conditions with SAA, indicating that HAv aβ2GPI, in the presence of physiological concentrations of acute-phase proteins represent pathogenic autoantibodies, which could lead to the development of premature atherosclerosis and/or thrombosis development.
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