Involvement of TLR2 and TLR4, <i>Chlamydophila pneumoniae</i> and <i>Mycoplasma pneumoniae</i> in adventitial inflammation of aortic atherosclerotic aneurysm

Abstract

Aortic atherosclerotic aneurysm (AAA) is associated with adventitial inflammation where infection is suggested to have a role. Co-infection withChlamydophila pneumoniae (Cp) and Mycoplasma pneumoniae (Mp) was linked with coronary plaque rupture, in association with vessel dilatation and adventitial inflammation. Pathogens are recognized by Toll-like receptors (TLRs) development of the inflammatory process. Objective: Here, we studied whether co-infection by Cp and Mp was involved in the increased inflammation present in AAA and if it could be associated with deficient expression of TLRs. We compared human samples of AAA with non-dilated human aortic atherosclerotic lesions, regarding the amount of Cp and Mp antigens, and expression of TLR2 and TLR4. Methods: Two groups of aorta fragments were analyzed: G1 (n = 13) moderate atherosclerosis and G2 (n = 14) AAA samples, through immunohistochemistry and in situ hybridization methods. Results: Mp and Cp antigens in intima/medial layer were greater in G2 than G1, with no difference in adventitia. TLR2 and TLR4 were higher in G2 than G1 adventitia fat. There was a correlation between Mp versus TLR2 and of TLR4 in intima/medial layer and in adventitia of G1, but there was a lack of correlation in G2. In Cp adventitia, the correlation in G1 was high with TLR2 but not with TLR4, and in G2 the correlation was positive for both TLRs. Conclusion: This study favors the concept that symbiotic co-infection by Cp and Mp participates in the pathogenesis of AAA. It also emphasizes that adventitial fat is the initial site for colonization of these bacteria that probably reach the tissue through vasa vasorum. An exacerbated immune reaction is not efficient to control the infection that reaches and proliferates in high levels at the medial and intimal layer, contributing to the development of vessel dilatation.

Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

“…S. sanguis , H. pylori , Staph aureus , bearing autoantigens such as the heat shock proteins HSP60, HSP70, was found in BS [ 72 ]. Chlamydia and Mycoplasma initially colonize the adventitia through vasa vasorum [ 116 ], whereas HSP60 and HSP 70 bind to EC and macrophages and induce the secretion of proinflammatory cytokines and MMPsin AAA [ 113 ]. Extracellular vesicles (EV), membrane-surrounded particles, modulate inflammation, vascular dysfunction, and thrombosis [ 117 ].…”

Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging

“…Remnants of more than 50 different viruses and bacteria were demonstrated in atherosclerotic plaques by polymerase chain reaction and hybridization of oligonucleotides with microbial ribosomal RNA, and no evidence was found for these organisms in normal arteries (237). Using electron microscopy and in situ hybridization, Mycoplasma pneumoniae and C. pneumoniae, and archaeal bodies were demonstrated within ruptured plaques (90), vulnerable plaques (91) and aortic aneurysms (206).…”

Oral PTCTS (Particulated Transialidase) Removes Serum Microparticles and Decreases Inflammation in Atherosclerotic Plaques of Rabbits

“…On the other hand, increased levels of MMP-9 are involved in degradation of this fibrous cap and segmental vessel dilatation, favoring plaque rupture [16] [17] and development of aneurysms [18]. In both situations, human studies from our lab found increased amount of microorganisms such as Mycoplasma pneumoniae and Chlamydophila pneumoniae [19], as well as activation of toll like receptors (TLR) 2 and 4 [20]. Antigens from Mycoplasma pneumoniae and oxLDL were found in increased levels in microparticles present in vulnerable plaques [21].…”