The influence of HIV infection on the correlation between plasma concentrations of monocyte chemoattractant protein-1 and carotid atherosclerosis

doi:10.1016/j.cca.2005.12.014

Clinica Chimica Acta

Volume 368, Issues 1–2, June 2006, Pages 114-119

https://doi.org/10.1016/j.cca.2005.12.014 Get rights and content

Abstract

Background

Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in atherosclerosis and it has been recently proposed as a surrogate biomarker of long-term clinical outcomes in patients with acute myocardial infarction. Little is known of the factors that may influence plasma MCP-1 concentrations.

Methods

We studied 384 healthy volunteers and 226 HIV-infected patients as a model of chronic inflammatory condition that predisposes to sub-clinical atherosclerosis.

Results

In healthy participants there were significant associations between plasma MCP-1 concentration and age, smoking status, and serum triglyceride concentrations that were not observed in the HIV-infected patients. The plasma concentration of MCP-1 was significantly associated with the polymorphism at position –2518 of the MCP-1 gene and, in patients, with the carotid artery intima–media thickness. There were also significant correlations indicating a close association between MCP-1 and HIV disease activity. However, in a multiple regression model, only age, the MCP-1 genotype and smoking status showed significant, and independent, associations with plasma MCP-1 concentrations.

Conclusion

Plasma MCP-1 concentration is genetically determined and associated with age and smoking habit and it also correlates with subclinical atherosclerosis in HIV-infected patients.

Introduction

Inflammation plays an important role in the development of atherosclerosis, and may be a predictive factor for the further progression of acute coronary syndromes [1], [2]. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine responsible for the recruitment of monocytes to sites of inflammation where they promote atherosclerotic lesions and plaque vulnerability [3], [4], [5]. The data obtained from clinical and experimental studies provide support for a role of MCP-1 on the initiation, and progression, of atherosclerosis [6], [7]. It is of note that plasma MCP-1 concentration seems to be genetically determined [8], and appears to be influenced by certain therapeutic agents and conditions such as myocardial infarction, hypertension, hypercholesterolemia and stroke [9], [10], [11], [12], [13], [14].

To further explore the relationship between plasma MCP-1 concentration and atherosclerosis, we sought associations with cardiovascular disease risk factors in a population-based sample of ostensibly healthy participants. We studied, as well, a group of HIV-infected patients since they are constantly challenged by various inflammatory stimuli which result in an imbalance in circulating cytokines [15]. In these patients, premature sub-clinical atherosclerosis is frequent and influenced by a mutant MCP-1 allele [16], [17]. As such, we hypothesize that there would be significant alterations in circulating markers of vascular inflammation such as C-reactive protein (CRP) and, as we currently propose, MCP-1. We also sought associations between these markers and the carotid intima–media thickness (CIMT), a well-validated surrogate marker for atherosclerotic vascular disease [18].

Section snippets

Study population

A population-based sample of 384 subjects (187 women, 197 men; mean age 42.1 years; range 19 to 75 years) was randomly selected from the local town hall's population register. The detailed characteristics have been presented elsewhere [19]. All the participants were of Mediterranean (Caucasian) ethnic origin, and were ostensibly healthy with no evidence of renal insufficiency, hepatic damage, cancer, or psychiatric disease that may alter their lifestyle habits. Also, there was no family history

Distribution of plasma MCP-1 concentrations

There were no statistically significant differences in plasma MCP-1 concentrations between males and females, nor in the healthy volunteers [median (inter-quartile range) 49.0 (25.7) ng/L and 48.3 (24.6) ng/L, respectively; P = 0.55] neither in the HIV-infected patients [median (inter-quartile range) 61.2 (38.5) ng/L and 56.4 (30.2) ng/L, respectively; P = 0.10]. Consequently, in all subsequent analyses data are presented without considering sex. The median MCP-1 concentration was 49.3 ng/L

Discussion

We have studied the association of plasma MCP-1 values with other relevant variables in a healthy population, and compared to a group of HIV-infected patients. Plasma MCP-1 concentration is regulated by genetic factors [8] and different inflammatory and/or oxidative conditions [10], [11], [12], [13], [14], [23]. Particularly, the presence of the G allele in the functional A-2518G MCP-1 promoter polymorphism influences the expression of MCP-1 and it has been shown to be associated with

Acknowledgements

Supported by grants from the FIS (00/0252 and 00/0954) of the Instituto de Salud Carlos III, the European Union and the Red de Centros de Metabolismo y Nutrición (C03/08), Madrid, Spain. NF and MT were recipients of grants from the Generalitat de Catalunya and BC from the ISCIII.

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The influence of HIV infection on the correlation between plasma concentrations of monocyte chemoattractant protein-1 and carotid atherosclerosis

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Distribution of plasma MCP-1 concentrations

Discussion

Acknowledgements

Clin Chim Acta

Immunol Today

Mol Cell

Biochem Biophys Res Com

Int J Cardiol

Am J Cardiol

Atherosclerosis

J Am Coll Cardiol

J Allergy Clin Immunol

Hum Immunol

Atherosclerosis

Blood

J Biol Chem

Clin Immunol Immunopathol

Gastroenterology

J Am Coll Cardiol

Atherosclerosis: an inflammatory disease

N Engl J Med

Macrophages, inflammation, and atherosclerosis

Int J Obes Relat Metab Disord