Vascular Endothelial Dysfunction in Inflammatory Bowel Diseases: Pharmacological and Nonpharmacological Targets

Abstract

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic inflammatory conditions involving primarily the gastrointestinal tract. However, they may be also associated with systemic manifestations and comorbidities. The relationship between chronic inflammation and endothelial dysfunction has been extensively demonstrated. Mucosal immunity and gastrointestinal physiology are modified in inflammatory bowel diseases, and these modifications are mainly sustained by alterations of endothelial function. The key elements involved in this process are cytokines, inflammatory cells, growth factors, nitric oxide, endothelial adhesion molecules, and coagulation cascade factors. In this review, we discuss available data in literature concerning endothelial dysfunction in patients affected by inflammatory bowel disease and we focus our attention on both pharmacological and nonpharmacological therapeutic targets.

Aortic Stiffening Is an Extraintestinal Manifestation of Inflammatory Bowel Disease: Review of the Literature and Expert Panel Statement

“…Tumor necrosis factor can also stimulate the production of matrix metalloproteinases (MMPs) and inhibit the tissue inhibitor of metalloproteinases, with subsequent production of uncoiled stiff collagen, degradation of elastin, and stiffening of the extracellular matrix. 26,68 In this regard, the collagenases MMP-1, MMP-8 and MMP-13, the gelatinase MMP-9, the stromelysin MMP-10, and the elastase MMP-12 are undetectable in the healthy gut and found in the actively inflamed intestine. 69 Considered together, current data suggest that several factors (including TNF, interleukins, asymmetric dimethyl arginine, and MMPs) play a role in the pathogenesis of endothelial dysfunction and arterial stiffening in patients with IBD.…”

“…69 Considered together, current data suggest that several factors (including TNF, interleukins, asymmetric dimethyl arginine, and MMPs) play a role in the pathogenesis of endothelial dysfunction and arterial stiffening in patients with IBD. 26,68…”

Takotsubo Syndrome and Inflammatory Bowel Diseases: Does a Link Exist?

“…However, literature data are extremely few. To the best of our knowledge, there are only 13 case reports (Tables 2, 3) describing the occurrence of TTS in IBD patients [26][27][28][29][30][31][32][33][34][35][36][37][38]. Interestingly, the totality of reported TTS occurred in female IBD patients.…”

“…None of the 4 UC patients with TTS were affected by active disease, neither treated by corticosteroids nor showing malabsorption (Table 3). Thus, it is difficult to find, on the basis of the only 4 reported cases, a specific pathophysiological mechanism for TTS among UC patients [35][36][37][38].…”

CU06-1004 Alleviates Experimental Colitis by Modulating Colonic Vessel Dysfunction

“…This increased vascular permeability reduces overall barrier function and allows for luminal bacteria-leukocyte interactions, which cause intestinal hypoxia and increased expression of free radicals and inflammatory cytokines, and lead to intestinal epithelial cell damage. Given that the upregulation of these adhesion molecules is linked to disease severity (Cromer et al, 2011;Alkim et al, 2015;Gravina et al, 2018;Sun et al, 2018), regulating these intestinal blood vessel changes is likely to be important for the prevention and treatment of IBD.…”