Abstract Body (Do not enter title and authors here): Background and hypothesis: Influenza is a significant public health and economic threat around the world. Although pneumonia is the most common complication associated with influenza, there are several clinical reports demonstrating increased risk for cardiovascular disease. Influenza infection induces interferons, proinflammatory cytokines and chemokines, and recruits’ macrophages and neutrophils to control the virus. However, an excessive influx of innate immune cells and dysregulated production of inflammatory mediators results in pathological responses during influenza infection. Studies have shown that influenza infection correlates with increased incidence of myocardial infarction. Atherosclerosis is the most known cause of ischemic heart diseases and stroke. Vascular cell adhesion molecule-1 (VCAM1) has been shown to promote adhesion of monocytes and promotes atherosclerosis. In this study, we hypothesize that VCAM1 plays a role in exacerbation of atherosclerosis during influenza infection.
Methods: High-Fat diet (HFD)-fed Apoe^-/- mice were infected with influenza A/PR/8/34 (H1N1) and weight loss, survival rate, and gene expression of vascular endothelial adhesion molecules, inflammatory cytokines and chemokines were measured. HFD-fed Apoe^-/- mice were infected with influenza, and treated with anti-VCAM1 antibody, and weight loss and cellular responses were measured.
Results and conclusions: Increased weight loss and decreased survival of mice were observed in response to influenza infection in HFD-induced atherosclerosis in Apoe^-/- mice. Further, the expression of VCAM1, and the levels of IL-6, CCL2, CCL3, CCL5 were significantly increased in aorta in Apoe^-/- mice when compared to PBS-treated controls. Increased survival, decreased weight loss, decreased lesion area, decreased frequency of CD11b⁺F4/80⁺Ly6C⁺, CD4⁺RORgt⁺ cells and increased frequency of CD4⁺FoxP3⁺ Treg cells were observed in aorta in response to antibody mediated VCAM1 neutralization. These results suggest that VCAM1 plays a pathological role in influenza-induced exacerbation of atherosclerosis.