CX3CR1 Receptor Polymorphisms, Th1 Cell Recruitment, and Acute Myocardial Infarction Outcome: Looking for a Link

Fractalkine is a proinflammatory chemokine that participates in atherosclerotic process mediating the interactions of vascular cells and leukocytes and selective recruitment of Th1 lymphocytes, through interaction with CX3CR1 receptor. The polymorphism of the fractalkine receptor 280M-containing haplotype, which codifies for a receptor with minor expression and with a reduced binding capability, represents a novel protective factor of atherosclerotic disease. We investigated the association among CX3CR1 genotype, the inflammatory infiltrate subpopulations recruited in the plaque, and the in situ expression of fractalkine and its receptor, in patients who died of myocardial infarction (AMI) compared with subjects who died of noncardiac causes. Patients with nonlethal AMI (AMI survivors) were also investigated to correlate the CX3CR1 polymorphisms and the incidence of lethal AMI. A strong T cells infiltrate was found in infarct related artery (IRA) plaques of AMI patients presenting the V249 T280 haplotype (84%). Conversely, a decreased T cell recruitment was associated with I249T280 haplotype in the controls (64%). The significant higher presence of the variant allele I249 in homo- and heterozygosis, found in controls (91%) and in AMI survivors (94%), with respect to the patients who died of AMI (48%), showed the relevance of this polymorphism both in the onset and outcome of acute myocardial infarction. The presence of CX3CR1 polymorphisms could influence the incidence and the outcome of acute myocardial infarction, altering the inflammation of the whole coronary tree by the impaired recruitment of Th1 polarized subpopulation in the coronary plaque.