(Circulation. 2000;102:1039.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E–Knockout Mice
From the Department of Pediatric Cardiology, Lund University Hospital (P.L., E.P.), and the Departments of Laboratory Animal Science (A.F.), Pathology (L.J.), and Medical Microbiology, University of Lund (T.W.), and Clinical Microbiology, Malmö (K.P.), Sweden; the Department of Pharmacology and Toxicology, University of Helsinki, Finland (P.K., I.P.); and the Department of Pathology, University of Lausanne, Switzerland (R.L.).
Correspondence to Dr Erkki Pesonen, Department of Pediatric Cardiology, Lund University Hospital, Lund 221 85, Sweden. E-mail erkki.pesonen{at}skane.se
Background—Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E–knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation.
Methods and Results—Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of NG-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P<0.05 and P<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME–pretreated aortas in infected mice at 2 weeks (P<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P<0.1). No intimal thickening was detected at either time point.
Conclusions—C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role of C pneumoniae infection in atherosclerosis development.
Key Words: endothelium • Chlamydia pneumoniae • nitric oxide • vasoconstriction
This article has been cited by other articles:
 |
|
 |
|
  E. Pesonen, E. Andsberg, A. Grubb, H. Rautelin, S. Meri, K. Persson, M. Puolakkainen, S. Sarna, and H. Ohlin Elevated infection parameters and infection symptoms predict an acute coronary event Therapeutic Advances in Cardiovascular Disease, December 1, 2008; 2(6): 419 - 424. [Abstract] [PDF]
|
|
|
|
 |
|
 I. Volanen, K. Kallio, M. Saarinen, M. J. Jarvisalo, R. Vainionpaa, T. Ronnemaa, J. Viikari, J. Marniemi, O. Simell, and O. T. Raitakari Arterial Intima-Media Thickness in 13-Year-Old Adolescents and Previous Antichlamydial Antimicrobial Use: A Retrospective Follow-up Study Pediatrics, September 1, 2008; 122(3): e675 - e681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Didion Chlamydophila pneumoniae and Endothelial Activation: The Smoke That Precedes the Fire of Atherosclerosis? Circ. Res., April 25, 2008; 102(8): 861 - 863. [Full Text] [PDF]
|
|
|
|
|
|
B. Schmeck, W. Beermann, P. D. N'Guessan, A. C. Hocke, B. Opitz, J. Eitel, Q. T. Dinh, M. Witzenrath, M. Krull, N. Suttorp, et al. Simvastatin Reduces Chlamydophila pneumoniae-Mediated Histone Modifications and Gene Expression in Cultured Human Endothelial Cells Circ. Res., April 25, 2008; 102(8): 888 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tormakangas, J. Ketonen, M. Leinonen, P. Saikku, and I. Paakkari Increased prostanoid dependency of arterial relaxation in Chlamydia pneumoniae-infected mice. J. Med. Microbiol., August 1, 2006; 55(Pt 8): 1017 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Volanen, M. J. Jarvisalo, R. Vainionpaa, M. Arffman, K. Kallio, S. Angle, T. Ronnemaa, J. Viikari, J. Marniemi, O. T. Raitakari, et al. Increased Aortic Intima-Media Thickness in 11-Year-Old Healthy Children With Persistent Chlamydia pneumoniae Seropositivity Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 649 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Charakida, A. E. Donald, M. Terese, S. Leary, J. P. Halcox, A. Ness, G. D. Smith, J. Golding, P. Friberg, N. J. Klein, et al. Endothelial Dysfunction in Childhood Infection Circulation, April 5, 2005; 111(13): 1660 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Berg, B. Maraha, A. van der Zee, S. K. Gielis, P. J. M. Roholl, G.-J. Scheffer, M. F. Peeters, and J. A. J. W. Kluytmans Effect of Clarithromycin Treatment on Chlamydia pneumoniae in Vascular Tissue of Patients with Coronary Artery Disease: a Randomized, Double-Blind, Placebo-Controlled Trial J. Clin. Microbiol., March 1, 2005; 43(3): 1325 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. de Kruif, E. C.M. van Gorp, T. T. Keller, J. M. Ossewaarde, and H. ten Cate Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research Cardiovasc Res, February 1, 2005; 65(2): 317 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. B Chesebro, E. Blessing, C.-C. Kuo, M. E Rosenfeld, M. Puolakkainen, and L. A. Campbell Nitric oxide synthase plays a role in Chlamydia pneumoniae-induced atherosclerosis Cardiovasc Res, October 15, 2003; 60(1): 170 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Liuba, J. Persson, J. Luoma, S. Yla-Herttuala, and E. Pesonen Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media Eur. Heart J., March 2, 2003; 24(6): 515 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Higgins Chlamydia pneumoniae and Coronary Artery Disease: The Antibiotic Trials Mayo Clin. Proc., March 1, 2003; 78(3): 321 - 332. [Abstract] [PDF]
|
|
|
|
|
|
M. Gervais, S. Pons, A. Nicoletti, C. Cosson, J.-F. Giudicelli, and C. Richer Fluvastatin Prevents Renal Dysfunction and Vascular NO Deficit in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 183 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Kalayoglu, P. Libby, and G. I. Byrne Chlamydia pneumoniae as an Emerging Risk Factor in Cardiovascular Disease JAMA, December 4, 2002; 288(21): 2724 - 2731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kohara, Y. Tabara, Y. Yamamoto, M. Igase, and T. Miki Chlamydia pneumoniae Seropositivity Is Associated With Increased Plasma Levels of Soluble Cellular Adhesion Molecules in Community-Dwelling Subjects: The Shimanami Health Promoting Program (J-SHIPP) Study Stroke, June 1, 2002; 33(6): 1474 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Parchure, E. G. Zouridakis, and J. C. Kaski Effect of Azithromycin Treatment on Endothelial Function in Patients With Coronary Artery Disease and Evidence of Chlamydia pneumoniae Infection Circulation, March 19, 2002; 105(11): 1298 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stenvinkel Endothelial dysfunction and inflammation--is there a link? Nephrol. Dial. Transplant., October 1, 2001; 16(10): 1968 - 1971. [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Streblow, S. L. Orloff, and J. A. Nelson Do Pathogens Accelerate Atherosclerosis? J. Nutr., October 1, 2001; 131(10): 2798S - 2804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.C. Kaski and E.G. Zouridakis Inflammation, infection and acute coronary plaque events Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I10 - I15. [Abstract] [PDF]
|
|
|
|
|
|
G. Caligiuri, M. Rottenberg, A. Nicoletti, H. Wigzell, and G. K. Hansson Chlamydia pneumoniae Infection Does Not Induce or Modify Atherosclerosis in Mice Circulation, June 12, 2001; 103(23): 2834 - 2838. [Abstract] [Full Text] [PDF]
|
|