| 1. |
- Liuba, Petru, et al.
(författare)
-
Acute Chlamydia pneumoniae infection causes coronary endothelial dysfunction in pigs.
- 2003
-
Ingår i: Atherosclerosis. - 1879-1484. ; 167:2, s. 215-222
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Coronary endothelial dysfunction contributes to the pathogenesis of acute coronary syndromes (ACSs). Acute Chlamydia pneumoniae infection has been epidemiologically associated with ACS. In this study, we investigated whether acute C. pneumoniae infection could alter the endothelial vasomotor function of porcine coronary vessels. Methods and results: Twenty pigs, 7–9 kg in weight, were inoculated intratracheally with C. pneumoniae (n=12) or saline (n=8), and investigated at 3 days (five infected/four non-infected) and 2 weeks (5+2 infected/four non-infected) after inoculation. The endothelium-dependent reactivity of coronary microcirculation was assessed at both time points by measuring peak coronary flow velocity (CFV) in response to bradykinin, before and after infusions with glutathione, an antioxidant, and Image-arginine, a substrate for nitric oxide synthase (NOS). CFV after bradykinin was significantly decreased in infected animals at both time points. At 2 weeks, both glutathione and Image-arginine significantly improved CFV after bradykinin. CFV after sodium nitroprusside (SNP) was similar in both groups. At 3 days, the relaxation responses of bradykinin-induced pre-contracted left anterior descending (LAD) coronary rings to bradykinin were significantly less in infected animals. NG-nitro-Image-arginine-methyl-ester, an NOS inhibitor, had significantly greater inhibitory effect on bradykinin-induced relaxation in infected animals. Plasma nitrate–nitrite and fibrinogen, and NOS activity from LAD coronary samples were significantly increased in infected animals. Conclusion: Acute C. pneumoniae infection causes endothelial dysfunction of both resistance and epicardial coronary vessels, and favours a pro-coagulant status. These effects could in part account for the epidemiologically suggested association between acute infection and ACS.
|
|
| 2. |
- Liuba, Petru, et al.
(författare)
-
Co-Infection with CHLAMYDIA PNEUMONIAE and HELICOBACTER PYLORI Results in Vascular Endothelial Dysfunction and Enhanced VCAM-1 Expression in ApoE-Knockout Mice.
- 2003
-
Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 40:2, s. 115-122
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> 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 <i>Chlamydia pneumoniae</i> and <i>Helicobacter pylori </i>on these two events in apoE-KO mice. <i>Methods:</i> Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either <i>C. pneumoniae</i> or <i>H. pylori,</i> while the 3rd group was infected with both <i>C. pneumoniae</i> and <i>H. pylori</i>. 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 <i>L</i>-NAME. The plasma levels of nitrate/nitrite were measured. <i>Results:</i> 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). <i>Conclusion:</i> Co-infection of apoE-KO mice with <i>C. pneumoniae</i> and <i>H. pylori</i> 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.
|
|
| 3. |
- Liuba, Petru, et al.
(författare)
-
Effects of Bradykinin on Aortic Endothelial Function in ApoE-Knockout Mice With Chronic Chlamydia Pneumoniae Infection.
- 2007
-
Ingår i: Circulation Journal. - : Japanese Circulation Society. - 1346-9843 .- 1347-4820. ; 71:9, s. 1480-1484
-
Tidskriftsartikel (refereegranskat)abstract
- Background Impaired muscarinic receptor-mediated vasodilation is an important feature of early atherosclerosis. Earlier studies on apolipoprotein E-knockout mice (apoE-KO) mice suggested adverse effects of Chlamydia pneumoniae infection on the endothelial vasomotor responses of aortas to the muscarinic agonist methacholine. Using additional aorta samples the present study investigated the responses to bradykinin. Methods and Results ApoE-KO mice were repeatedly inoculated with either Chlamydia pneumoniae (C. pneumoniae) or saline. At 2, 6, and 10 weeks after the first inoculation, precontracted aorta rings from both groups were exposed to bradykinin in the absence and presence of L-NAME and diclofenac. In noninfected animals, the vasomotor responses to bradykinin were similar at all timepoints (p > 0.5). Compared with noninfected animals, the responses in infected animals tended to increase through the study period (p < 0.05 at 10 weeks). Although diclofenac and L-NAME had no effect in noninfected mice, they inhibited the responses to bradykinin in infected mice at 6 and, more markedly, 10 weeks (p < 0.05 for both). Conclusion Bradykinin stimulation of aorta endothelium from C. pneumoniae-infected apoE-KO animals appears to activate compensatory kinin receptor-related mechanisms that could involve nitric oxide and vasorelaxing prostanoids. Although the precise molecular mechanisms require further investigation, one could speculate that strategies increasing bradykinin availability might reverse the arterial dysfunction during chronic infectious disease.
|
|
| 4. |
- Liuba, Petru, et al.
(författare)
-
Protective effects of simvastatin on coronary artery function in swine with acute infection.
- 2006
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 186:2, s. 331-336
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine. Methods: Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneunioniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pretreated with simvastatin (80 mg daily), while the remaining animals received placebo. The treatment was started 2 weeks prior to inoculation and Continued until the end of the Study. ANOVA was used for statistical calculations. Data are mean +/- S.D. Results: All animals inoculated with C. pneumoniae developed IgM antibodies against this organism. As compared to noninfected animals, peak-to-baseline coronary flow velocity (CFV) ratio after bradykinin was significantly decreased in infected animals regardless of statin treatment (1,p=0.01). Intracoronary 10(-6) M acetylcholine caused slight dilatory responses in both noninfected and infected-treated animals (CFV ratio: 1.6 +/- 0.2and 1.4 +/- 0.2, respectively: p > 0.1),while a velocity drop (CFV ratio: 0.7 +/- 0.1; p < 0.01 versus noninfected-infected and treated). indicating constriction, was observed in in fected-non treated animals; 10(-5) M acetylcholine caused vasoconstriction in all animals, with a significantly more prolonged response in the infected-non treated group (p < 0.01). Intracoronary adenosine and SNP induced similar dilatory responses in all groups (p > 0.5). There were no differences in markers of systemic inflammation (fibrinogen, amyloid, and CRP) and lipid profile (HDL, LDL and total cholesterol) between the groups (p > 0.2). Conclusion: Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
|
|
