HYPERTENSION-RELATED IMPAIRMENT OF MESENTERIC ENDOTHELIAL FUNCTION CONTRIBUTES INTO GUT-LIVER AXIS VIA INTESTINAL DYSBIOSIS AND HEPATIC STEATOSIS, AND ASSOCIATES WITH GENETIC DYSRE

Abstract

Objective: Metabolic violations, obesity and other related comorbidities are obvious in arterial hypertension. It is known that Hepatic Steatosis (HS) and Arterial hypertension (AH) has to some extend common pathogenesis realized through metabolic and immune mechanisms involving vascular and digestive system injury, and forming Gut-Liver axis, which remain mostly untouched in recent studies. We aimed on evaluating the endothelial function and mesenteric vessels remodeling depending on I/D polymorphism of angiotensin-converting enzyme (ACE) gene and A1166C polymorphism of angiotensin II type 1 receptor (AGTR1) gene in hypertensive patients with HS. Design and method: Study included 104 AH patients with HS (50 females, 54 males, age 53.2±8.7). Intimae-media thickness (IMT) of abdominal aorta (AO) and other flow mediated parameters of mesenteric vessels state evaluated by sonography. NO (nitrite/nitrate) plasma concentration, vascular adhesive molecule (sVCAM-1) level were defined by IEA. ACE (I/D) and AGTR1 (A1166C) genes polymorphisms assessed with PCR. Results: High risk of endothelial dysfunction (ED) is: D-allele of ACE gene (p<.001); C-allele of AGTR1 gene (p = .02). In DD-genotype were higher flow-mediated parameters of mesenteric vessels. IMT of AO was thicker in CC-genotype of AGTR1 gene (p = .039-.01) and independent on I/D genotypes of ACE gene. sVCAM-1 level was higher (p<.01) in D-allele of ACE gene, than in II-genotype and not depending on A1166C polymorphism of AGTR1 gene. NO plasma level doesn’t depend on ACE (I/D) and AGTR1 (A1166C) genes polymorphisms. Vascular remodeling in HS patients (AO IMT enlargement for more than 0.9 mm) is associated with dysbiosis III-IV grades’ and sVCAM-1 plasma level growth by 1,3-1,6 times (p<.05-.001). AO IMT correlates with dysbiosis severity, presence of HS and sVCAM-1 level and is independent from AH severity. Conclusions: Risk contingents for endothelial dysfunction and mesenteric vessels remodeling in HS patients are: by sVCAM-1 plasma level and diameter of mesenteric vessels increasing – DD-genotype carriers of ACE gene; by IMT of abdominal aorta enlargement – CC-genotype carriers of AGTR1 gene (p<0.02-0.001).