A possible role for CCR5 in the progression of atherosclerosis in HIV-infected patients: a cross-sectional study

作者：Fernandez Sender Laura; Alonso Villaverde Carlos; Rull Anna; Rodriguez Gallego Esther; Riera Borrull Marta; Hernandez Aguilera Anna; Camps Jordi; Beltran Debon Raul; Aragones Gerard; Menendez Javier A; Joven Jorge^*

来源：AIDS Research and Therapy, 2013, 10(1): 11.

DOI：10.1186/1742-6405-10-11

• Cardiovascular risk factors
• Chemokine receptors
• Genetic variants
• Inflammation
• Maraviroc

Background: Chemokines can block viral entry by interfering with HIV co-receptors and are recognised mediators of atherosclerosis development. A number of experimental drugs that inhibit HIV entry arrest the development of atherosclerosis in animal models. We hypothesised that the expression of chemokine receptors in circulating leukocytes is associated with the rate of atherosclerosis progression in HIV-infected patients.
Methods: The increase in intima-media thickness during a 2-year follow-up was used to classify HIV-infected patients (n = 178) as progressors (n = 142) or non-progressors (n = 36) with respect to atherosclerosis. Logistic regression was used to assess variables associated with atherosclerosis progression. Mutations in the CCR5 Delta 32, CCR2 64I, and CX3CR1 (T280M and V249I) co-receptors as well as the levels of CCR5, CXCR4, CX3CR1, and CCR2 mRNA expression in circulating leukocytes were analysed as independent variables.
Results: Among the baseline variables, only genetic variants explained the dichotomous outcome. The expression of CCR2 and CXCR4 did not discriminate between progressors and non-progressors. Conversely, CCR5 and CX3CR1 expression was higher in not only progressors but also patients with detectable viral load. The logistic regression, however, demonstrated a significant role for CCR5 expression as a predictor of atherosclerosis progression (B = 2.1, OR = 8.1, p = 0.04) and a negligible effect for CXC3R1 and CCR2 expression.
Conclusions: Available CCR5 antagonists should be investigated for their potential to delay the course of atherosclerosis in HIV-infected patients.

• 出版日期2013-5-9