Co-infection with Chlamydia pneumoniae and Helicobacter pylori results in vascular endothelial dysfunction and enhanced VCAM-1 expression in apoE-knockout mice.
BACKGROUND
Upregulation of proinflammatory endothelial cell adhesion molecules and decreased bioactivity of endothelial nitric oxide (NO) are important in the pathogenesis of atherosclerosis. We investigated the effects of co-infection with Chlamydia pneumoniae and Helicobacter pylori on these two events in apoE-KO mice.


METHODS
Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either C. pneumoniae or H. pylori, while the 3rd group was infected with both C. pneumoniae and H. pylori. Mice from the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal aortas were harvested after 10 weeks, and staining for vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to methacholine were studied in organ chambers in the absence and presence of L-NAME. The plasma levels of nitrate/nitrite were measured.


RESULTS
Staining for VCAM-1 was more intense at the branching sites of aortas from mice with co-infection than in mono-infected or noninfected apoE-KO mice. The relaxation responses to methacholine and the plasma levels of nitrate/nitrite were significantly less in the co-infected group than in the other groups (p < 0.05).


CONCLUSIONS
Co-infection of apoE-KO mice with C. pneumoniae and H. pylori seems to be associated with impaired bioactivity of endothelial NO and increased expression of VCAM-1 at branching sites. The findings may suggest an additive interaction of these pathogens in atherogenesis.
Liuba
Petru
P
Department of Pediatric Cardiology, Lund University Hospital, Lund, Sweden. Petru.Liuba@pedi.lu.se
Pesonen
Erkki
E
Paakkari
Ilari
I
Batra
Satish
S
Andersen
Leif
L
Forslid
Anders
A
Ylä-Herttuala
Seppo
S
Persson
Kenneth
K
Wadström
Torkel
T
Wang
Xin
X
Laurini
Ricardo
R
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001057:Apolipoproteins E / Q000235:genetics*; D002690:Chlamydia Infections / Q000378:metabolism / Q000503:physiopathology*; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D004269:DNA, Bacterial / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016481:Helicobacter Infections / Q000378:metabolism / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000907:Antibodies, Bacterial; D001057:Apolipoproteins E; D004269:DNA, Bacterial; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester