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Cardiovascular Research 2003 60(1):170-174; doi:10.1016/S0008-6363(03)00389-4
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Nitric oxide synthase plays a role in Chlamydia pneumoniae-induced atherosclerosis

Brian B Chesebro1, Erwin Blessing2, Cho-Chou Kuo, Michael E Rosenfeld, Mirja Puolakkainen3 and Lee Ann Campbell*

Department of Pathobiology, University of Washington, P.O. Box 357238, Seattle, WA 98195, USA

*Corresponding author. Tel.: +1-206-543-0317; fax: +1-206-543-3873. Email address: bchesebr{at}mail.jhmi.edu, lacamp{at}u.washington.edu

Received 23 October 2002; accepted 7 April 2003


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Objective: Chlamydia pneumoniae infection has been associated with atherosclerosis, although the mechanisms by which C. pneumoniae contribute to atherogenesis remain unclear. Altered production of nitric oxide, a known bactericidal and anti-inflammatory agent, represents one possible mechanistic link. To examine this issue, a diet-induced, hyperlipidemic mouse model of early atherosclerosis was used. Methods: A series of intranasal inoculations of C. pneumoniae strain AR-39 were administered to mice lacking endothelial or inducible nitric oxide synthase and to normal controls. After 18 weeks on an atherogenic diet, atherosclerotic lesion area in the aortic sinus was measured using computer-assisted morphometry. Results: In the absence of C. pneumoniae infection, diet-fed eNOS–/– mice developed enlarged fatty streak lesions of borderline significance in comparison to uninfected, wild-type mice, while the lesion area in uninfected, diet-fed iNOS–/– mice did not differ significantly from lesion area in wild-type animals. In contrast, lesion area in infected eNOS–/– mice increased slightly, but not significantly in comparison to uninfected eNOS–/– mice. Lesion area in the infected iNOS–/– mice was significantly enlarged when compared to both uninfected iNOS–/– mice as well as to infected wild-type mice. Conclusions: These data suggest that production of nitric oxide by eNOS protects against development of fatty streak lesions in uninfected hyperlipidemic mice, but does not offer additional protection in infected hyperlipidemic mice, while iNOS may play a protective role, thus limiting chlamydial exacerbation of fatty streak lesions.

KEYWORDS Infection/inflammation; Atherosclerosis; Nitric oxide; Histopathology; Coronary artery disease


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
The development of atherosclerosis is generally believed to begin with some form of vessel wall injury and the associated inflammatory response [1]. Recently, infectious agents such as Chlamydia pneumoniae and cytomegalovirus have been associated with coronary artery disease (CAD) and atherosclerosis [2]. The association of C. pneumoniae and atherosclerosis has been well documented by seroepidemiologic studies [3], detection of organisms in atheromas [4] and therapeutic trials [5]. The use of mouse models has shown that C. pneumoniae infection accelerates the development of atherosclerosis in hypercholesterolemic mice [6–8]. However, C. pneumoniae infection in the absence of hyperlipidemia does not induce atherosclerosis in mouse models demonstrating that C. pneumoniae and hyperlipidemia are co-risk factors for atherosclerotic lesion development [7,9,10]. Nevertheless, the precise role of C. pneumoniae in atherosclerosis is unknown.

One possible link between atherosclerosis and C. pneumoniae infection involves the production of nitric oxide (NO) from a family of enzymes called nitric oxide synthase (NOS). Two prominent isoforms of NOS detected in blood vessels are endothelial NOS (eNOS) and inducible NOS (iNOS). eNOS is constitutively expressed in normal vascular endothelial cells and exerts an anti-atherogenic effect through the generation of NO involved in vasodilation as well as inhibition of leukocyte adhesion, platelet adhesion and smooth muscle cell proliferation [11]. In early atherosclerotic lesions, endothelial dysfunction with a concomitant decrease in eNOS has been observed which may lead to vasoconstriction, inflammation, thrombosis and migration of proliferative smooth muscle cells [11,12]. In contrast, iNOS expression can be induced in a variety of cell types including macrophages, vascular smooth muscle cells (VSMC) and endothelial cells in response to inflammation and cytokine release. In more advanced atherosclerotic lesions, increased iNOS expression in VSMC and macrophages has also been noted [13,14]. In such inflammatory environments, NO can react with superoxide to form peroxynitrite, a highly reactive oxidant that, in turn, leads to the oxidation of LDL and the formation of foam cells [15]. Interestingly, iNOS expression can also be induced by chlamydial infection, and iNOS has anti-microbial activity against chlamydia [16–19].

Possibly, C. pneumoniae infection might influence atherosclerosis by altering the expression or activity of iNOS and/or eNOS. In recent experiments using ApoE knockout mice, which develop accelerated atherosclerosis, C. pneumoniae infection led to a reduced bioavailability of endothelial NO, thereby significantly impairing endothelium-dependent vasorelaxation [20]. However, the subsequent impact of NO on C. pneumoniae-related atherosclerosis has not yet been examined directly. In this study, the respective roles of eNOS and iNOS in C. pneumoniae-related exacerbation of fatty streak development were investigated by using eNOS knockout (eNOS–/–) and iNOS knockout (iNOS–/–) mice fed an atherogenic diet.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1 Mouse models and C. pneumoniae inoculation
Eight-week old, pathogen-free, male C57BL/6J mice as well as eNOS–/– and iNOS–/– mice on a C57BL/6J background were obtained from Jackson Laboratories (Bar Harbor, ME). Mice were fed an atherogenic diet consisting of 15% fat, 1.25% cholesterol and 0.5% sodium cholate for 18 weeks beginning at 8 weeks of age. Ten mice from each group (C57BL/6J, eNOS–/–, iNOS–/–) were inoculated intranasally with 2.4 x 107 inclusion forming units (IFU) of C. pneumoniae strain AR-39 at 8, 9 and 10 weeks of age. Ten control mice from each group were sham-inoculated with sterile phosphate buffered saline. Prior to each infection, mice were mildly sedated by intraperitoneal injections of a mixture of ketamine and xylazine. The mice were euthanized at 26 weeks of age for examination of fatty streak development. At necropsy, the mice were sedated with a mixture of 15 mg/kg Acepromazine Maleate and 150 mg/kg Ketamine HCl and blood was collected by exanguination from the femoral arteries. This study conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).

2.2. Serology and lipid measurements
Plasma was separated from heparinized blood and frozen at –70°C for serology and lipid measurements. C. pneumoniae-specific antibody titers from sera collected 18 weeks post-inoculation were determined by the microimmunofluorescence test using formalin-fixed C. pneumoniae elementary bodies as antigen. Total blood cholesterol was measured using a commercial enzymatic test kit (Sigma, St. Louis, MO). Values were determined in triplicate.

2.3. Measurement of lesion area
Because the aortic sinus is the site most prone to develop atherosclerosis in C57BL/6J mice [21], lesions at the aortic sinus were measured exclusively. Freshly frozen tissue sections throughout the aortic sinus were prepared as previously described [8]. Tissue sections were stained with Oil Red O and the lesion areas were measured from 15 stepped sections with computer-assisted morphometry using ImageProPlus 4.1 software. The average lesion area per section per mouse was then calculated. All measurements were performed in a blinded fashion with the investigator unaware of the group of the specimen. Statistical analysis was performed using the nonparametric Mann–Whitney U-test.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Monitoring of infection
To confirm that mice were indeed infected, C. pneumoniae-specific antibodies were measured and acute clinical signs were observed. Clinical signs in infected mice included: tachypnea, naso-ocular discharge and decreased body weight. These signs were observed 2–3 days after each inoculation and disappeared within 1 week. All infected mice developed an IgG antibody response, while all control mice remained antibody negative (Table 1). These combined data indicate that all inoculated mice had been infected with C. pneumoniae, while all control mice were negative.


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  		Table 1 Serum cholesterol levels and antibody titers against Chlamydia pneumoniae in infected and uninfected C57BL/6J, iNOS–/– and eNOS–/– mice

 
3.2. Cholesterol measurements
To determine the respective impact of eNOS–/–, iNOS–/– and C. pneumoniae infection on lipid profiles in diet-induced, hyperlipidemic animals, cholesterol levels were measured in sera collected at 18 weeks post-inoculation. There were no significant differences among any of the experimental groups (Table 1) indicating that serum cholesterol levels were not altered by C. pneumoniae infection, eNOS or iNOS.

3.3 Effect of eNOS–/– and iNOS–/– on fatty streak development in uninfected mice
Due to the relevance of NOS enzymes in vascular physiology, the independent effects of eNOS–/– and iNOS–/– on fatty streak development were analyzed. In the absence of C. pneumoniae infection, diet-fed eNOS–/– mice developed enlarged fatty streaks in comparison to uninfected C57BL/6J mice, although this enlargement was of borderline significance (P = 0.054) (Fig. 1). Conversely, uninfected, diet-fed iNOS–/– mice did not develop enlarged lesions when compared to diet-fed C57BL/6J mice (Fig. 1).


Figure 1
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  		Fig. 1 The effect of Chlamydia pneumoniae infection on fatty streak development in hyperlipidemic C57BL/6J, iNOS–/– and eNOS–/– mice. Mice were inoculated intranasally with 2.4 x 107 inclusion forming units of C. pneumoniae (strain AR-39) at 8, 9 and 10 weeks of age. Control mice were sham-inoculated with sterile PBS. An atherogenic diet was started in conjunction with the first inoculation (8 weeks of age) and continued for 18 weeks (26 weeks of age). Average lesion area per aortic sinus tissue section was measured by computer-assisted morphometry following Oil Red O staining. The solid bar indicates uninfected animals and the open bar represent infected mice. Bar graphs indicate means±S.E.M. P values were calculated using the nonparametric Mann–Whitney U-test. ({dagger}, P<0.05 vs. uninfected C57BL/6J; *, P<0.01 vs. uninfected iNOS–/–; **, P<0.02 vs. infected C57BL/6J; {ddagger}, P = 0.054 vs. uninfected C57BL/6J).

 
3.4 Effect of eNOS–/– and iNOS–/– on fatty streak development in C. pneumoniae infected mice
In order to examine the interplay between NOS and C. pneumoniae infection as manifested in atherosclerotic pathology, eNOS–/– and iNOS–/– mice on an atherogenic diet were infected with C. pneumoniae. Lesion area in infected eNOS–/– mice increased slightly, but not significantly, when compared to uninfected eNOS–/– animals (Fig. 1). However, C. pneumoniae infection led to significantly enlarged lesions in diet-fed C57BL/6J and iNOS–/– mice as compared to uninfected C57BL/6J and iNOS–/– mice, respectively (P<0.05 and P<0.01). The lesions in the infected iNOS-/- animals were also significantly larger than those found in the infected C57BL/6J animals (P<0.02), suggesting a protective role for iNOS against C. pneumoniae-related fatty streak formation.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The production of NO in the vasculature is a complex and multifaceted process that has important implications for vascular biology and pathophysiology. Several animal studies support the protective role of eNOS in atherosclerotic disease. In the present study, uninfected eNOS–/– developed enlarged fatty streaks in comparison to uninfected C57BL/6J mice. Kuhlencordt et al. recently reported the significant enlargement of atheromas in apoE–/–/eNOS–/– mice as compared to apoE–/–/eNOS+/+ mice [22]. Thus, the combined findings of these two animal studies appear to indicate that impairment of eNOS activity is important throughout the developmental stages of atherogenesis.

Our results show that C. pneumoniae did not augment lesion progression in hyperlipidemic eNOS–/– mice. This result is in contrast to the significant enlargement of lesions in C. pneumoniae infected C57BL/6J mice observed both in this study as well as in another previously published report [8]. Although lesion areas for infected eNOS–/– mice were comparable to those of infected iNOS–/– mice, eNOS must have additional effects apart from those involving C. pneumoniae because lesion areas were already elevated in uninfected eNOS–/– animals. Thus, it appears that eNOS exerts a protective effect in uninfected hyperlipidemic mice but does not afford additional protection in C. pneumoniae infected hyperlipidemic mice.

Several animal model studies support the hypothesis of iNOS-mediated oxidative stress as a pathogenic mechanism of atherosclerosis. In the present study, a diet-induced hyperlipidemic C57BL/6J mouse model was used to examine the independent effect of iNOS on early (fatty streak formation), as opposed to late (developed atheroma), atherogenesis. Our results are in agreement with those of Niu et al. who also found no lesion enlargement in diet-fed iNOS–/– animals [23]. However, independent reports using apoE/iNOS double knockout mice on a Western-type diet each show a reduction of atherosclerotic lesion area in the mice lacking iNOS which suggests a pro-atherogenic role for iNOS in this animal model [24,25]. Our finding, in conjunction with these animal studies, implicates iNOS activity in late-stage atherosclerosis, while iNOS in early atherogenesis appears to have no significant effect on disease pathology and progression.

A significant increase in lesion area in infected iNOS–/– mice was observed in comparison to uninfected iNOS–/– mice as well as to infected C57BL/6J mice. These results suggest that iNOS plays a protective role against C. pneumoniae-related fatty streak formation.

Although no change in total plasma cholesterol levels was observed, it does not exclude that there was not effect on the distribution of different lipoproteins because NO can react with superoxide to peroxynitrite, which can lead to oxidation of LDL (15). Because of the time course of infection, measurements of iNOS were not performed because any transient increase in iNOS expression induced by C. pneumoniae would likely have occurred well before the animals were sacrificed. It is also likely that the oxidative stress and inflammatory activation accompanying the hypercholesterolemia would have already maximally induced iNOS in the arterial macrophages.

Several in vitro studies implicate iNOS activity as an important anti-chlamydial defense mechanism. In cultured epithelial cells, cytokine-induced iNOS activity leads to a reduced infectivity of both C. pneumoniae and C. trachomatis [16,17]. As with these in vitro experiments, animal studies also support an in vivo role for iNOS as a mediator of defense against chlamydial infection. For instance, studies have shown an increase in C. pneumoniae lung load in iNOS–/– mice following intranasal inoculation [18] as well as increased rates of urogenital disease in C. trachomatis infected iNOS–/– mice [19]. The present study provides further evidence of the importance of iNOS in limiting the pathologic effects of C. pneumoniae infection in early atherosclerosis. Presumably, enhanced C. pneumoniae infection occurs in iNOS–/– animals with impaired innate immunity. The increased bacterial load or persistent infection could then lead to subsequent enhancement of pro-atherogenic mechanisms such as C. pneumoniae induction of foam cell formation [26] and/or increased metalloprotease expression and activity [27] above and beyond the exacerbations observed in infected wild-type animals.

Nevertheless, because iNOS activity has been shown to be pro-atherogenic in later stage atherosclerosis through a hypothesized increase in oxidative stress and peroxynitrite formation, the impact of C. pneumoniae infection and iNOS on more advanced lesions can not be predicted. While the present study demonstrates a protective role for iNOS in fatty streak C. pneumoniae-related atherosclerosis, further studies should be conducted using apoE/iNOS double knockout animals to discern the interplay between C. pneumoniae and iNOS in more advanced atherosclerotic lesions.


   Acknowledgements
 
This study was supported by NIH grant HL-56036. BB Chesebro was supported by a Fellowship from the Sarnoff Endowment for Cardiovascular Science.


   Notes
 
1 Current address: School of Medicine, Johns Hopkins University, Baltimore, MD 21287. USA. Back

2 Current address: Ruprecht-Karl-Universitat Heidelberg, Bergheimer Strasse 58, 69115 Heidelberg, Germany. Back

3 Current address: University of Helsinki, Haartman Institute, Department of Virology, P.O. Box 21 (Haartmaninkatu 3), 00014 University of Helsinki, Finland. Back

Time for primary review 34 days.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med (1999) 340:115–126.[Free Full Text]
  2. O'Connor S., Taylor C., Campbell L.A., Epstein S., Libby P. Potential infectious etiologies of atherosclerosis: a multifactorial perspective. Emerg Infect Dis (2000) 7:780–789.[Web of Science]
  3. Saikku P., Mattila K., Nieminen R.S., et al. Serological evidence of an association of a novel chlamydia. TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet (1988) 2:983–986.[Web of Science][Medline]
  4. Kuo C.-C., Shor A., Campbell L.A., et al. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis (1993) 167:841–849.[Web of Science][Medline]
  5. Gurfinkel E., Bozovich G., Daroca A., Beck E., Mautner B. Randomized trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. ROXIS study group. Lancet (1997) 350:404–407.[CrossRef][Web of Science][Medline]
  6. Moazed T.C., Campbell L.A., Rosenfeld M.E., Grayston J.T., Kuo C.C. Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in ApoE-deficient Mice. J Infect Dis (1999) 180:238–241.[CrossRef][Web of Science][Medline]
  7. Hu H., Pierce G.N., Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest (1999) 103:747–753.[Web of Science][Medline]
  8. Blessing E., Campbell L.A., Rosenfeld M.E., Chough N., Kuo C. Chlamydia pneumoniae infection accelerates hyperlipidemia induced atherosclerotic lesion development in C57BL/6J mice. Atherosclerosis (2001) 158:13–17.[CrossRef][Medline]
  9. Blessing E., Lin T.-M., Campbell L.A., Rosenfeld M., Kuo C.-C. Chlamydia pneumoniae induces inflammatory changes in hearts and aortas of C57B1/6 mice. Infect Immun (2000) 68:4765–4868.[Abstract/Free Full Text]
  10. Blessing E., Campbell L.A., Rosenfeld M.E., Kuo C.-C. Chlamydia pneumoniae infection prior to induction of hyperlipidemia does not accelerate development of atherosclerotic lesion in C57BL/6J mice. Infect Immun (2002) 70:5332–5334.[Abstract/Free Full Text]
  11. Loscalzo J., Welch G. Nitric oxide and its role in the cardiovascular system. Prog Cardiovasc Dis (1995) 38(2):87–104.[CrossRef][Web of Science][Medline]
  12. Oemar B.S., Tschudi M.R., Godoy N., et al. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation (1998) 97:2494–2498.[Abstract/Free Full Text]
  13. Wilcox J., Subramanian R., Sundell C., et al. Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol (1997) 17:2479–2488.[Abstract/Free Full Text]
  14. Behr D., Rupin A., Fabiani J.N., Verbeuren T.J. Distribution and prevalence of inducible nitric oxide synthase in atherosclerotic vessels of long-term cholesterol-fed rabbits. Atherosclerosis (1999) 142:335–344.[CrossRef][Web of Science][Medline]
  15. Graham A., Hogg N., Kalyanaraman B., et al. Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor. FEBS Lett (1993) 330:181–185.[CrossRef][Web of Science][Medline]
  16. Igietseme J.U., Ananaba G.A., Candal D.H., Lyn D., Black C.M. Immune control of chlamydial growth in the human epithelial cell line RT4 involves multiple mechanisms that include nitric oxide induction, tryptophan catabolism and iron deprivation. Microbiol Immunol (1998) 42:617–625.[Web of Science][Medline]
  17. Matsushima H., Shirai M., Ouchi K., et al. Lymphotoxin inhibits Chlamydia pneumoniae growth in Hep-2 cells. Infect Immun (1999) 7:75–79.
  18. Rottenberg M.E., Gigliotti-Rothfuchs A.C., Gigliotti D., et al. Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice. J Immunol (1999) 162:2829–2830.[Abstract/Free Full Text]
  19. Ramsey K.H., Miranpuri G.S., Sigar M., Ouellette S., Byrne G.I. Chlamydia trachomatis persistence in the female mouse genital tract: inducible nitric oxide synthase and infection outcome. Infect Immun (2001) 69:5131–5137.[Abstract/Free Full Text]
  20. Liuba P., Karnani P., Pesonen E., et al. Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice. Circulation (2000) 102:1039–1044.[Abstract/Free Full Text]
  21. Paigen B., Morrow A., Holmes P.A., Mitchell D., Williams R.A. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis (1987) 68:231–240.[CrossRef][Web of Science][Medline]
  22. Kuhlencordt P.J., Gyurko R., Han F., et al. Accelerated atherosclerosis, aortic aneurysm formation and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double knockout mice. Circulation (2001) 104:448–454.[Abstract/Free Full Text]
  23. Niu X.L., Yang X., Hoshiai K., et al. Inducible nitric oxide synthase deficiency does not effect the susceptibility of mice to atherosclerosis but increases collagen content in lesions. Circulation (2001) 27(103):1115–1120.
  24. Kuhlencordt P.J., Chen J., Han F., Astern J., Huang P.L. Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation (2001) 103:3099–3104.[Abstract/Free Full Text]
  25. Detmers P.A., Hernandez M., Mudgett J., et al. Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice. J Immunol (2000) 165:34303435.
  26. Kalayoglu M.V., Byrne G.I. Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis (1998) 177:725–729.[Web of Science][Medline]
  27. Kol A., Sukhoua G.K., Lichtman A.H., Libby P. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor alpha and matrix metalloproteinase expression. Circulation (1998) 98:300–307.[Abstract/Free Full Text]

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