Abstract
Background:Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion. Genetic variation in the CARD15 gene, which encodes NOD2, was previously shown to result in a barrier defect that causes chronic inflammatory disorders (e.g. Crohn disease). In the present study, we investigated the possible involvement of NOD2/CARD15 in the pathology of CHD by i) analyzing the local expression of NOD2 in atherectomy versus healthy tissue (n = 5 each) using histochemical immunofluorescence and ii) by testing the three major functional CARD15 variants (R702W, G908R and 1007fs) for association with early-onset CHD in 900 German patients and 632 healthy controls.Results:In atherectomy tissue of CHD patients, NOD2 was detected in inflammatory cells at the luminal sides of the lesions. However, the allele and genotype frequencies of the three major CARD15 polymorphisms did not differ between CHD patients and controls.Conclusion:The NOD2 up-regulation in atheroma lesions indicates an involvement of this protein in the pathology of CHD. Although NOD2 could be important in local immune response mechanisms, none of the analyzed CARD15 variants seem to play a significant role in the etiology of CHD.
Highlights
Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients
Impairment of mucosal barriers could be a key factor in the pathogenesis of CHD as it allows bacteria to invade from body surfaces into systemic circulation and to colonize the atherosclerotic lesion
We investigated the occurrence and frequencies of the three most common polymorphisms in the CARD15 gene that are associated with mucosal barrier dysfunction (R702W, G908R and 1007fs) in a sample of patients with CHD (n = 900) and compared the results to those obtained from healthy controls (n = 632)
Summary
Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. It has become apparent that inflammation is a driving factor in the pathophysiology of coronary heart disease (CHD). BMC Genetics 2007, 8:76 http://www.biomedcentral.com/1471-2156/8/76 cal and animal studies that bacterial infection may be involved in the pathophysiology of the local chronic inflammatory process underlying atherosclerosis [6,7,8,9]. Impairment of mucosal barriers could be a key factor in the pathogenesis of CHD as it allows bacteria to invade from body surfaces into systemic circulation and to colonize the atherosclerotic lesion
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