Cardiovascular manifestations of inflammatory bowel diseases and the underlying pathogenic mechanisms

Inflammatory bowel disease (IBD), consisting of ulcerative colitis and Crohn's disease, mainly affects the gastrointestinal tract but is also known to have extraintestinal manifestations because of long-standing systemic inflammation. Several national cohort studies have found that IBD is an independent risk factor for the development of cardiovascular disorders. However, the molecular mechanisms by which IBD impairs the cardiovascular system are not fully understood. Although the gut-heart axis is attracting more attention in recent years, our knowledge of the organ-to-organ communication between the gut and the heart remains limited. In patients with IBD, upregulated inflammatory factors, altered microRNAs and lipid profiles, as well as dysbiotic gut microbiota, may induce adverse cardiac remodeling. In addition, patients with IBD have a three- to four times higher risk of developing thrombosis than people without IBD, and it is believed that the increased risk of thrombosis is largely due to increased procoagulant factors, platelet count/activity, and fibrinogen concentration, in addition to decreased anticoagulant factors. The predisposing factors for atherosclerosis are present in IBD and the possible mechanisms may involve oxidative stress system, overexpression of matrix metalloproteinases, and changes in vascular smooth muscle phenotype. This review focuses mainly on 1) the prevalence of cardiovascular diseases associated with IBD, 2) the potential pathogenic mechanisms of cardiovascular diseases in patients with IBD, and 3) adverse effects of IBD drugs on the cardiovascular system. Also, we introduce here a new paradigm for the gut-heart axis that includes exosomal microRNA and the gut microbiota as a cause for cardiac remodeling and fibrosis.