Molecular analysis of aortic intimal hyperplasia caused by Porphyromonas gingivalis infection in mice with endothelial damage.
OBJECTIVE
Porphyromonas gingivalis infection is thought to be a significant etiological factor in the development of cardiovascular diseases. However, scant definitive evidence has been presented concerning the pathological molecular mechanisms of these disorders. In the present study, we performed a molecular analysis of the developmental mechanisms of aortic intimal hyperplasia induced by P. gingivalis.


METHODS
The effects of P. gingivalis-induced bacteremia on intimal hyperplasia were evaluated using a mouse model of aortic hyperplasia created by photochemical-induced endothelial cell injury. Alterations of gene expression profiles in injured blood vessels of the mice were extensively analyzed using DNA microarray assays to identify the key molecules involved in P. gingivalis-induced hyperplasia. In addition, human aneurismal specimens from patients with or without P. gingivalis infection were analyzed histochemically.


RESULTS
Intravenous administration of P. gingivalis dramatically induced intimal hyperplasia in the mouse model. Concomitantly, S100 calcium-binding protein A9 (S100A9) and embryonic isoform of myosin heavy chain (SMemb), a proliferative phenotypic marker of smooth muscle cells, were significantly overexpressed on the surfaces of smooth muscle cells present in the injured blood vessels. Similarly, increased expressions of S100A9 and SMemb proteins were observed in aneurismal specimens obtained from P. gingivalis-infected patients.


CONCLUSIONS
We found that bacteremia induced by P. gingivalis leads to intimal hyperplasia associated with overexpressions of S100A9 and SMemb. Our results strongly suggest that oral-hematogenous spreading of P. gingivalis is a causative event in the development of aortic hyperplasia in periodontitis patients.
Hokamura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Inaba
H
H
Nakano
K
K
Nomura
R
R
Yoshioka
H
H
Taniguchi
K
K
Ooshima
T
T
Wada
K
K
Amano
A
A
Umemura
K
K
D000818:Animals; D001011:Aorta / Q000382:microbiology* / Q000473:pathology; D001014:Aortic Aneurysm / Q000382:microbiology / Q000473:pathology; D050197:Atherosclerosis / Q000382:microbiology / Q000473:pathology; D016470:Bacteremia / Q000382:microbiology; D016866:Bacteroidaceae Infections / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D040502:Calgranulin B / Q000032:analysis; D019742:Chemokines, CC / Q000032:analysis; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries* / Q000382:microbiology; D005263:Femoral Artery / Q000293:injuries / Q000382:microbiology; D006801:Humans; D006965:Hyperplasia; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D018995:Myosin Heavy Chains / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D020033:Protein Isoforms / Q000032:analysis; D013290:Streptococcal Infections / Q000473:pathology; D013295:Streptococcus mutans / Q000472:pathogenicity; D017539:Tunica Intima / Q000382:microbiology* / Q000473:pathology
D015415:Biomarkers; D040502:Calgranulin B; C095218:Ccl9 protein, mouse; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D020033:Protein Isoforms; C070959:Ccl6 protein, mouse; D018995:Myosin Heavy Chains