Exploring the Role of Gut Vascular Barrier Proteins in HIV-Induced Mucosal Damage: A Comparative Study.

Abstract

This study aims to compare intestinal mucosal damage and the expression levels of occludin, zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, β-catenin, and plasmalemma vesicle-associated protein (PLVAP) in the gut vascular barrier (GVB) among people living with HIV (PLWH), asymptomatic PLWH, and healthy volunteers (non-PLWH). Three groups were selected for the study: PLWH, asymptomatic PLWH, and healthy volunteers. Colonic mucosal tissue samples were collected via colonoscopy from all participants. Histological examination of the colonic mucosa was conducted using hematoxylin and eosin staining. The expression levels of occludin, ZO-1, VE-cadherin, β-catenin, and PLVAP were assessed using RT-qPCR, immunohistochemistry, and western blot analyses. Pathological scores of colonic mucosa in PLWH and asymptomatic PLWH were significantly higher than those in non-PLWH (p < .001 and p = .0056, respectively). CD4⁺ T cell counts in asymptomatic PLWH and non-PLWH were significantly higher than in PLWH (p < 0.05). The CD4⁺/CD8+ T cell ratio in non-PLWH significantly exceeded those in PLWH and asymptomatic PLWH (p < .05). Analysis of protein and mRNA expression revealed: (1) no statistically significant differences in PLVAP-mRNA expression across all groups (p > .05); (2) higher PLVAP protein levels in PLWH compared with asymptomatic PLWH and non-PLWH (p < .05), with no significant differences between asymptomatic PLWH and non-PLWH (p = .632); (3) significantly higher PLVAP expression in the colonic mucosa of PLWH and asymptomatic PLWH compared with non-PLWH (p = .034 and p = .011, respectively), with no significant differences between PLWH and asymptomatic PLWH (p > .999). ZO-1 expression was significantly lower in PLWH than in non-PLWH (p = .012), with no notable differences between asymptomatic PLWH and other groups. PLWH, compared with healthy controls, exhibit significant inflammatory changes in the intestinal mucosa. PLVAP expression serves as a potential indicator to assess the extent of GVB damage and disease progression in PLWH.