Abstract WP439: Hiv-associated Brain Arterial Remodeling Is Correlated With Increased Mmp-2 Expression: A Pilot Study.

Abstract

Listen

Translate article

Introduction: The pathophysiology of stroke in HIV involves alterations in vessel wall structure, both inward (stenosis) and outward remodeling (dilatation). Metalloproteinase-2 (MMP-2) has been implicated in the remodeling of large arteries, but it has not been studied in the cerebral arteries. Objectives: To assess the potential role of MMP-2 in brain arterial remodeling in HIV infection. Methods: Circle of Willis arteries were obtained from 38 brain donors with and without HIV infection, autopsied by the Manhattan HIV Brain Bank. The lumen-to-wall-ratio (LWR) was obtained from transversal Van Gieson stains and used to assess remodeling with larger ratios indicating outward remodeling. Immunohistochemistry was used to assess MMP-2 expression in the arterial wall, scored as average pixel intensity and expressed as arbitrary units (AU). Demographic and clinical variables were used as covariates of remodeling in linear regression models. Results: The sample included 38 middle cerebral arteries from 28 individuals with HIV and 10 without. Compared to non-HIV controls, the HIV group was younger (57 vs. 45 years, P=0.001), more frequently male (40 vs. 70 %, P=0.08) and African American (43 vs. 20%, P=0.18), but reported less hypertension (50 vs. 25%, P=0.14) and diabetes (66 vs. 33%, P=0.03). The expression of MMP-2 was higher in the HIV group (171 vs. 186 AU, P=0.14). After adjusting for age, sex, ethnicity, hypertension and diabetes, subjects with HIV had higher LWR (β=4.7, P=0.03, R 2 =0.22), although adjusting for MMP-2 reduced the strength of the association (β= 3.7, P=0.20, R 2 =0.52). Stratifying by HIV status, MMP-2 was the only significant predictor of outward remodeling in the HIV group (P=0.02). In this group, age >45 years (P=0.005), CD4 count <200 (P=0.005) and hypertension (P=0.07) were predictors of greater MMP-2 expression. The numbers were too small to assess the role of MMP-2 in individuals without HIV. Conclusion: MMP-2 may be associated with outward remodeling of cerebral arteries in HIV-infected individuals, particularly in the context of hypertension and immunosuppression. More studies are needed to better understand this arterial physiopathology given the increased cerebrovascular disease seen in the HIV-infected population.