Atherosclerosis in patients infected with HIV is influenced by a mutant monocyte chemoattractant protein-1 allele.
ABSTRACT Patients infected with HIV present with premature atherosclerosis, and the 2 diseases share common pathogenic pathways. We investigated mutations in the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known to control aspects of these pathways, to ascertain whether they are involved in atherogenesis in these patients.
We performed carotid and femoral artery ultrasonography to detect subclinical atherosclerosis in patients infected with HIV (n=183). MCP-1-2518G and CCR-2 64I polymorphisms were determined in the HIV group and in a population-based control group (n=348). We also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1-2518G in the group of patients with subclinical atherosclerosis was significantly higher than in patients without atherosclerotic lesions (47.5% versus 18.2%, respectively; P<0.001). Furthermore, the patients with atherosclerotic lesions had higher MCP-1 plasma concentrations than did patients without lesions (74.15 [4.03] versus 57.81 [3.67] pg/mL, respectively; P=0.03). When adjusted for known cardiovascular risk factors, the MCP-1-2518G allele was associated with subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80, P=0.004). Compared with measurements conducted approximately 2.5 years earlier in a subset of 40 patients, intima-media thickness (IMT) in the carotid artery progressed at a mean rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele (P=0.08).
HIV-infected patients with the MCP-1-2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.
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ABSTRACT: Atherosclerosis is an inflammatory disease in which several chemokines are implicated. The roles of these molecules extend from the recruitment of circulating inflammatory cells to the activation of inflammatory and pro-thrombotic cascades, which ultimately leads to an atherosclerosis-related event. One of the most studied chemokines is monocyte chemoattractant protein-1 (CCL2), which has been strongly linked to atherosclerosis in both animal and human studies. The higher the expression of either the CCL2 gene or its receptor CCR-2, the higher the likelihood of developing atherosclerosis in genetically-modified animals. Conversely, the deletion of either CCL2 or its receptor is followed by a significant reduction in the development of atherosclerotic plaques. Studies in humans yield controversial results. Most of these studies linked the plasma CCL2 concentration to the occurrence of atherosclerosis or related events; however, this relationship does not seem to be independent of the classical, known risk factors. Currently, there are no suitable analytical tools to reach strong conclusions with respect to the value of plasma CCL2 concentration as a biomarker of atherosclerosis, but experimental evidence suggests that the CCL2/CCR2 pathway should be further explored as a diagnostic, prognostic and therapeutic target.Clinica Chimica Acta 09/2007; 383(1-2):21-9. DOI:10.1016/j.cca.2007.04.019 · 2.76 Impact Factor
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ABSTRACT: HIV-infected patients are known to be at risk for premature coronary artery disease. This emerging paradigm is a rising concern for clinicians. Due to advances in the treatment of HIV, this once fatal infection has been transformed into a chronic illness. Traditional risk factors paired with the long-term use of antiretroviral therapy (ART) and chronic inflammation leads to premature atherosclerosis, particularly progression of atherosclerotic plaque. This population of patients requires early recognition of subclinical atherosclerosis, as well aggressive primary and secondary prevention strategies among the multi-disciplinary team of physicians caring for them. We sought to present a comprehensive review of the available literature related to HIV and atherosclerosis and cardiovascular risk.American Journal of Cardiovascular Drugs 02/2015; 15(2). DOI:10.1007/s40256-015-0105-8 · 2.20 Impact Factor