The risk of cardiovascular complications in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic, relapsing disease of unknown etiology involving gastrointestinal tract. IBD comprises two main entities: ulcerative colitis and Crohn's disease. Several studies showed increased risk of cardiovascular complications in chronic inflammatory disorders, especially during IBD relapses. Endothelium plays a role in physiologic regulation of vascular tone, cell adhesion, migration and resistance to thrombosis. Also, its dysfunction is associated with increased risk of atherosclerosis development. There are several potential links between chronic IBD-related inflammatory processes and the risk of cardiovascular disease, but insight into pathogenetic pathways remains unclear. We present the current concepts and review of adult and pediatric studies on the risk of CVD in IBD.

Keywords: Atherosclerosis; Endothelial dysfunction; Inflammatory bowel disease; Ischemic heart disease.

Fig. 1

Potential pathogenesis of atherosclerosis and inflammatory processes in IBD. In intestinal inflammatory diseases, several pathways lead to increased bacterial exposure, including disruption of the mucous layer, dysregulation of epithelial tight junctions, increased intestinal permeability, and increased bacterial adherence to epithelial cells. In IBD, innate cells produce proinflammatory cytokines: TNF-α, interleukin-1β, interleukin-6, interleukin-12, interleukin- 23, and chemokines. There is also an increase in CD4+ T cell levels, especially in proinflammatory T-cell subgroups, which secrete proinflammatory cytokines and chemokines. Increased production of chemokines results in recruitment of additional leukocytes, which leads to cycle of inflammation. Monocytes recruited through the activated endothelium differentiate into macrophages. Several endogenous and microbial molecules can ligate pattern-recognition receptors (toll-like receptors) on these cells, inducing activation which results in release of inflammatory cytokines, chemokines, oxygen and nitrogen radicals, and other inflammatory molecules. This leads to inflammation and tissue damage. Antigens presented by macrophages and dendritic cells (antigen-presenting cells) trigger the activation of antigen-specific T cells in the artery. Most of the activated T cells produce Th1 cytokines which activate macrophages and vascular cells, leading to inflammation. Regulatory T cells modulate the process by secreting anti-inflammatory cytokines (such as interleukin-10 and transforming growth factor b). Adopted from Abraham and Hannson [16, 17]