Influence of congenital and infective factors on the progression of atherosclerotic disease
Based on literature data and our previous studies it seemed reasonable that a pattern recognition molecule (mannan binding lectin)---or rather its genetically defective mutant form---which takes role in the innate immunity may contribute in the progression of severe atherosclerosis. We also wondered if this molecule, which is able to activate the complement system, has any role at an other vascular territory of the arterial system (carotid artery).
Our work was to investigate the relation of Chlamydia and the mannan binding lectin for the first time in vascular disease. The mutant variant has lower plasma concentration of the functionally active mannan binding lectin protein and seemed to put the patients under 2-3 times higher risk for having coronary artery disease and for developing severe complication in anti-Chlamydia positive individuals. This correlation was existed even after adjustment for sex, age, smoking habits and total cholesterol level. There were no correlation among patients carrying homozygote wild genotype (A/A).
Patients carrying the wild A allele develop restenosis after eversion type carotid endarterectomy more frequently as our retrospective analysis revealed. This effect seemed to be gene-dose dependent: patients with the homozygote variant allele (O/O) are to be more protected compared to heterozygotes. None of the 6 patients carrying homozygote genotype has had developed restenosis.
According to the data of the prospective study a higher degree of restenosis was present in women carrying the homozygote wild allele (A/A) compared to the A/O and O/O genotype at 7 month postoperatively and they kept on having this tendency all the way. Significant difference could be measured only at the end of the follow-up in men.
Deficient mannan binding lectin has a lower affinity to microorganism and carries a higher chance for the inflammation to stay chronically and may contribute to the development of vascular wall inflammation. On the contrary high levels of mannan binding lectin may cause tissue destruction through complement activation.