Chlamydia pneumoniae Causes Abdominal Aortic Aneurysm

An aortic aneurysm is a bulging out in a segment of the largest artery in the body, the aorta. Infections have long been known to cause inflammation and aneurysm of the aorta: about 66% of patients with chronic syphilis [aka Treponema pallidum] develop aortic aneurysms. However, since antibiotics have been available to treat this infection, syphilitic aneurysms have become rare, and the health establishment has pretended that, therefore, infection is seldom involved anymore. It is acknowledge that aortic aneurysm is common (10%) in patients with Takayasu's arteritis, and arteritis common in patients with other so-called autoimmune diseases (10-15% of giant cell arteritis, 5% of rheumatoid patients, 2-5% of Reiter's syndrome, and 1-10% of spondyloarthropathy patients). Abdominal aortic aneurysm is more common in men than in women. The inflammation in AAA is primarily in the middle and outer of the three layers of the artery, in contrast to atherosclerosis in which the inner and middle layers are mainly affected, and to giant cell arteritis, in which primarily the outermost layer is involved.

Antibodies to Chlamydia pneumoniae are rarely found in children less than five years old; the primary infection usually occurs between ages 8 and 16. Reinfections occur throughout childhood, and the rate of infection is higher among men than women. In non-elderly people it causes mild respiratory symptoms, but may cause pneumonia in the elderly. Indications of the presence of Chlamydia pneumoniae have been found in the majority of studies which have looked for them. Odds ratios for Cpn and abdominal aortic aneurysm have exceeded 5, which is high enough to cause confounding by infection. This means that studies which ignore the role of infection will falsely implicate smoking and other non-causal factors, due to higher exposure to infection in people of lower socioeconomic classes, which adjustment by proxy variables such as income does not eliminate. {See Confounding By Infection.)

C pneumoniae was found in 11/25 aortas, 5/9 iliac arteries, 2/5 femoral arteries, and 1/2 iliac veins, by PCR in AAA specimens. It was also seen in vascular tissue from 3/6 "ostensibly normal" liver transplant donors, which showed some atherosclerotic changes. "The figures are perhaps conservative as it is possible that more specimens would be found to be C pneumoniae positive if a larger amount of tissue was examined." (Detection and widespread distribution of Chlamydia pneumoniae in the vascular system and its possible implications. G Ong, BJ Thomas, AO Mansfield, BR Davidson, D Taylor-Robinson. J Clin Pathol 1996 Feb;49(2):102-106).

Ong - J Clin Pathol 1996 abstract / PubMed

In this study, 12 out of 12 consecutive patients who were operated on for AAA were positive for Chlamydia pneumoniae by immunohistochemistry. (Immunohistochemical detection of Chlamydia pneumoniae in abdominal aortic aneurysms. J Juvonen, T Juvonen, A Laurila, H Alakarppa, K Lounatmaa, H-M Surcel, M Leinonen, MI Kairaluoma, P Saikku. Ann NY Acad Sci 1996 Nov 18;800:236-238.) (No abstract)

26/51 AAA surgery patients were positive for C pneumoniae by PCR. (Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms. F Blasi, F Denti, M Erba, R Cosentini, R Raccanelli, A Rinaldi, L Fagetti, G Esposito, U Ruberti, L Allegra. J Clin Microbiol 1996 Nov;34(11):2766-2769.)

Blasi / J Clin Microbiol 1996 full article
Blasi - J Clin Microbiol 1996 abstract / PubMed

C pneumoniae-specific antigens were found in 12/12 aneurysm specimens by immunohistochemistry, and in 8/12 by PCR; C pneumoniae DNA was found in 6/6 by PCR; C pneumoniae elementary bodies were found in 3/4 by electron microscopy. No control samples were positive. (Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms. J Juvonen, T Juvonen, A Laurila, H Alakarppa, K Lounatmaa, H-M Surcel, M Leinonen, P Saikku. J Vasc Surg 1997 Mar;25(3):499-505.) They also noted that "Despite the direct evidence on the presence of C pneumoniae in all 12 patients with abdominal aortic aneurysm, one patient had no C pneumoniae antibodies, and two had only low titers present in the sera," similar to earlier findings in atherosclerosis.

Juvonen - J Vasc Surg 1997 abstract / PubMed

C pneumoniae-specific DNA was found in 14/40 AAA specimens, versus 2/40 controls. (Chlamydia pneumoniae in human abdominal aortic aneurysms. E Petersen, J Boman, K Persson, C Arnerlov, G Wadell, P Juto, A Eriksson, G Dahlen, KA Angquist. Eur J Vasc Endovasc Surg 1998 Feb;15(2):138-142.)

Petersen - Eur J Vasc Surg 1998 abstract / PubMed

This is one of only a few studies failing to detect evidence of C pneumoniae in AAA, 0/20. "Minor inhibition of the PCR was noticed especially in media specimens." (Failure to demonstrate Chlamydia pneumoniae in symptomatic abdominal aortic aneurysms by a nested polymerase chain reaction (PCR). JS Lindholt, L Ostergard, EW Henneberg, H Fasting, P Andersen. Eur J Vasc Endovasc Surg 1998 Feb;15(2):161-164.)

Lindholt - Eur J Vasc Endovasc Surg 1998 abstract / PubMed

(Immunoglobulin A antibodies against Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysm. JS Lindholt, S Juul, S Vammen, I Lind, H Fasting, EW Henneberg. Br J Surg 1999 May;86(5):634-638.) They note, "In fact, direct detection of C pneumoniae antigens in DNA in lesions seems more frequent in people with low rather than high titres. This is contrary to a dose-response reaction, which could have been expected. Chronic infection has the potential to produce progressive arterial degradation but can persist only when there is an insufficient immunological response. While high titres may be found in patients with past infections that were sufficiently eradicated by the immunological system, infections with low titres are more likely to be chronic. Consequently, a dose-response effect cannot be expected, and direct detection of DNA could be negative compared with the traditionally used high titres." [And vice versa. And, the issue of whether high or low titres are characteristic in recurrent herpes zoster, where the causal role of the virus is not in dispute, is still not entirely resolved, so this one could be unsettled indefinitely.]

Lindholt - Br J Surg 1999 abstract / PubMed

C pneumoniae antigen was found in 6/11 AAA samples by immunohistological staining. Lymphocytes were cultured from 17/22 AAA samples, and 8 of the 17 were responsive to C pneumoniae. "The presence of mononuclear lymphocytes in chronic inflammation of the AAA tissue is an indication of a specific immune response, but the specific antigen or antigens inducing this response have not been determined... The target antigen of these antibodies has been characterized as a microfibrillar component that can also be bound by anti-Treponema pallidum or herpes simplex specific antibodies, indicating that microbial infections may play a role in inducing the development of autoimmune antibodies." "Thus, these data suggest that C pneumoniae, which is frequently found in aneurysm tissue, is not a passive resident in the damaged vessel wall but contributes to the maintenance of the inflammatory reaction." (Chlamydia pneumoniae reactive T lymphocytes in the walls of abdominal aortic aneurysms. S Halme, T Juvonen, A Laurila, J Juvonen, M Mosorin, P Saikku, H-M Surcel. Eur J Clin Invest 1999 Jun;29(6):546-552.)

This study also contrasted the proliferative response of T-cell lines from peripheral blood versus those from aneurysmal tissue. Even more provocatively, it demonstrated high rates of reactivity of those aneurysmal T-cell lines to antigens from Chlamydia trachomatis and PPD (Mycobacterium tuberculosis antigens, to which persons exposed to other Mycobacterial species may also react). This suggests that history of exposure to certain other infections besides C pneumoniae is an important factor. And, smokers are more likely to be exposed to many infections for socioeconomic reasons.

Halme - Eur J Clin Invest 1999 abstract / PubMed

This study found C pneumoniae antigens in 19/19 and lipopolysaccharide in 15/19, but not DNA by ISH or PCR. They also found both C pneumoniae and herpes simplex antigens together in 10/19. (Chlamydia pneumoniae in abdominal aortic aneurysms. Abundance of membrane components in the absence of heat shock protein 60 and DNA. A Meijer, JA van der Vliet, PJM Roholl, SK Gielis-Proper, A de Vries, JM Osseward. Arterioscler Thromb Vasc Biol 1999 Nov;19(11):2680-2686.)

Meijer / Arterioscler Thromb Vasc Biol 1999 full article
Meijer - Arterioscler Thromb Vasc Biol 1999 abstract / PubMed

20/41 consecutive AAA surgery specimens were CP+ by PCR. (Chlamydia pneumoniae DNA detection in peripheral blood mononuclear cells is predictive of vascular infection. F Blasi, J Boman, G Esposito, G Melissano, R Chiesa, R Cosentini, P Tarsia, Y Tshomba, M Betti, M Alessi, N Morelli, L Allegra. J Infect Dis 1999 Dec;180(6):2074-2076.)

Blasi - J Infect Dis 1999 abstract / PubMed

C pneumoniae was detected in 20/26 AAA specimens by immunohistochemistry, versus 1/17 controls. Notably, C pneumoniae was cultured from 10 of the 20. It is notoriously difficult to culture. (Detection of viable Chlamydia pneumoniae in abdominal aortic aneurysms. L Karlsson, J Gnarpe, J Naas, G Olsson, J Lindholm, B Steen, H Gnarpe. Eur J Vasc Endovasc Surg 2000 Jun;19(6):630-635.)

Karlsson - Eur J Vasc Endovasc Surg 2000 abstract / PubMed

As usual, an anti-smoking junk science study does not attempt to look for an infectious cause, such as this typical example which was published in the supposedly prestigious American Journal of Epidemiology of The Johns Hopkins University School of Hygiene and Public Health: Risk factors for aortic aneurysm: Results of a case-control study. JF Blanchard, HK Armenian, PP Friesen. Am J Epidemiol 2000 Mar 15;151(6):575-583.

Blanchard - AJE 2000 abstract / PubMed

They breezily dismissed the possibility that they might have left out an important risk factor: "Inclusion of AAA cases due to causes such as trauma or infection could influence observed associations. However, since these are rare causes of AAA [sic - this means the few traditionally accepted infectious causes -cast] and we did not knowingly include any such cases in our study, we expect that this would have had a minor effect on our results." It is not clear how their ignorance of such cases would prevent confounding. They smugly proclaimed, "As has been reported in several previous studies, we found that smoking is a dominant risk factor for AAA. The strength and dose-response of the association between the cumulative lifetime history of cigarette smoking and AAA suggest a causal role for cigarette smoking in the etiology of AAA." They do not attempt any explanatory mechanism whereby smoking supposedly causes a focal lesion with bacteria within it which are merely innocent bystanders.

Their deceitful treatment of this subject is particularly egregious because in 1998, Blanchard et al presented a paper, "The relationship between Chlamydia pneumoniae infection and abdominal aortic aneurysm," at the Proceedings of the 9th International Symposium on Human Chlamydial Infection in San Francisco. And, evidently from the same study of 98 cases and 102 controls, they published a paper, "The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm: Case-control study" (Clin Infect Dis 2000 Jun;30(6):946-947). This latter version of the study found an adjusted OR of 5.97 for Chlamydia pneumoniae by serology, and they admitted that "infection with C. pneumoniae may play a role in the pathogenesis of abdominal aortic aneurysm."

Blanchard - CID 2000 abstract / PubMed

But smoking was not discussed in this study. This means that in the typical anti-smoker review, consisting of a literature search only for studies that present results for smoking, with little or no attention to the role of infection, the anti-smoking study in the American Journal of Epidemiology will be counted as "evidence," while the one in Clinical Infectious Diseases will not be.

Detection of Chlamydia pneumoniae DNA in buffy-coat samples of patients with abdominal aortic aneurysm. B Maraha, M den Heijer, M Wullink, A van der Zee, A Bergmans, H Verbakel, M Kerver, S Graafsma, S Kranendonk, M Peeters. Eur J Clin Microbiol Infect Dis 2001 Feb;20(2):111-116. CP DNA in 18/88 (20%) of patients vs 8/88 (9%) of controls, adjusted OR = 2.9, 95% CI 1-8.5; IgG antibodies to CP in 85/88 (97%) of patients vs 71/88 (81%) of controls, adjusted OR 7.2, 95% CI 1.7-31. NOTE THAT ADJUSTMENT IS LIKELY TO CAUSE CONFOUNDING AND WEAKENING OF THE ASSOCIATION.

Maraha - Eur J Clin Microbiol Infect Dis 2001 abstract / PubMed

Antibodies against Chlamydia pneumoniae predict the need for elective surgical intervention on small abdominal aortic aneurysms. S Vammen, JS Lindholt, PL Andersen, EW Henneberg, L Ostergaard. Eur J Vasc Endovasc Surg 2001 Aug;22(2):165-168. "IgG antibodies measured by ELISA were most predictive"

Vammen - Eur J Vasc Endovasc Surg 2001 abstract / PubMed

Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms. JS Lindholt, HA Ashton, RA Scott. J Vasc Surg 2001 Aug;34(2):212-215. "An IgG titer of 128 or more was present significantly more often in cases with an expansion greater than 1 cm annually (adjusted OR = 12.6; 95% CI 1.37-293)."

Lindholt - J Vasc Surg 2001 abstract / PubMed

Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. M Mosorin, J Juvonen, F Biancari, J Satta, HM Surcel, M Leinonen, P Saikku, T Juvonen. J Vasc Surg 2001 Oct;34(4):606-610. At 18 months, "The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group." Also, C-reactive protein levels in the doxycycline group were significantly lower.

Mosorin - J Vasc Surg 2001 abstract / PubMed

[The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm.] A Wolski, E Mazur, J Niedzwiadek, J Slepko, M Koziol-Montewka, J Michalak. Pol Merkuriusz Lek 2001 Dec;11(66):491-494. "Serologic markers of persistent C. pneumoniae infection have been detected in 25/28 (89.3%) patients and in 6/20 (30%) healthy controls. In 40% (10/25) of patients with serologic markers of persistent C. pneumoniae infection high titers of specific IgG and IgA indicated active infection -- reinfection or exacerbation of chronic infection. Mean concentrations of IL-10, IL-12, IFN-gamma and TNF-alpha indicated lack of protection against intracellular pathogens. Since all patients in this group were diagnosed as having symptomatic AAA, we suggest that active infection can exacerbate inflammation in the AAA wall and accelerate progression of the disease. In our opinion patients with active C. pneumoniae infection may be candidates to the antimicrobial treatment."

Wolski - Pol Merkuriusz Lek 2001 abstract / PubMed

[Submitral annular aneurysm, postpartum cardiomyopathy, and Chlamydia pneumoniae antibodies in Niamey (Niger)] A Cenac, C Chaineau, JM Sueur, J Orfila. Med Trop 2002 Mar;62(1):81-84. "Findings showed that all three patients with annular submitral left ventricular aneurysm had significantly elevated plasma IgG and IgA anti-Chlamydia pneumoniae antibody levels at the time of diagnosis."

Cenac - Med Trop 2002 abstract / PubMed

Chlamydia pneumoniae in atherosclerotic lesions of patients undergoing vascular surgery. F Loehe, I Bittmann, C Weilbach, L Lauterjung, FW Schildberg, MM Heiss. Ann Vasc Surg 2002 Jul;16(4):467-473. This study claimed to find no correlation between clinical or laboratory parameters of atherosclerosis and detection of C. pneumoniae - which would not be surprising if CP were involved in all cases but was not detected in some.

Loehe - Ann Vasc Surg 2002 abstract / PubMed

Lack of association between serum immunoreactivity and Chlamydia pneumoniae detection in the human aortic wall. M Porqueddu, R Spirito, A Parolari, M Zanobini, G Pompilio, G Polvani, F Alamanni, D Stangalini, E Tremoli, P Biglioli. Circulation 2002 Nov 19;106(21):2647-2648.

Porqueddu - Circulation 2002 / Full Article

Chlamydia pneumoniae in patients undergoing surgery for thoracic aortic disease. C Nystrom-Rosander, E Hjelm, A Lukinius, G Friman, L Eriksson, S Thelin. Scand Cardiovasc J 2002 Dec;36(6):329-335. "A high prevalence of serum IgA antibodies to C. pneumoniae was found in TAA patients. In contrast no signs of C. pneumoniae were detected in patients with thoracic aortic dissection."

Nystrom-Rosander - Scand Cardiovasc J 2003 abstract / PubMed

Anti chlamydia antibodies in patients with thoracic and abdominal aortic aneurysms. M Schillinger, H Domanovits, W Mlekusch, K Bayegan, G Khanakah, AN Laggner, E Minar, G Stanek. Wien Klin Wochenschr 2002 Dec 30;114(23-24):972-977. "Thoracic aortic aneurysms were not associated with signs of Chlamydia infection or immunopathogenicity. In contrast, patients with abdominal aortic aneurysms exhibited elevated levels of immunoglobulin against Chlamydial LPS, reflecting an unspecific Chlamydia pathogenicity."

Schillinger - Wien Klin Wochenschr 2002 abstract / PubMed

A review of macrolide treatmwnt of atherosclerosis and abdominal aortic aneurysm. JS Lindholt, J Stovring, PL Andersen, EW Henneberg, L Ostergaard. Curr Drug Targets Infect Disord 2003 Mar;3(1):55-63. Studies to date have been small, but most show benefit of antimicrobial treatment.

Lindholt - Curr Drug Targets Infect Disord 2003 abstract / PubMed

Immunofluorescence in situ and the serologic indices of Chlamydia pneumoniae infection in patients with abdominal aortic aneurysm. A Wolski, E Korobowitz, Z Siezieniewska, E Mazur, J Niedzwiadek, M Koziol-Montewka, J Michalak. Pol J Pathol 2003;53(4):223-228.

Wolski - Pol J Pathol 2003 abstract / PubMed

The detection of Chlamydia pneumoniae in aneurysm of abdominal aorta and in normal aortic wall of organ donors. A Pupka, J Skora, G Kaluza, P Szyber. Folia Microbiol (Praha) 2004;49(1):79-82. "In symptomatic aneurysms, DNA was found in 9 cases (29%) and in ruptured aneurysms in 14 cases (49%). In the control group, C. pneumoniae was not detected in the aortic wall."

Pupka - Folia Microbiol (Praha) 2004 abstract / PubMed

Detection of C. pneumoniae by polymerase chain reaction-enzyme immunoassay in abdominal aortic aneurysm walls and its association with rupture. BL Cheuk, AC Ting, SW Cheng. Eur J Vasc Endovasc Surg 2005 Feb;29(2):150-155. In aortic walls collected consecutively from 30 patients with intact AAA, 16 patients with ruptured AAA and 19 healthy organ donors (control), "C. pneumoniae DNA was detected more frequently in patients with aneurysms, particular with ruptured aneurysms. The incidence of positive C. pneumoniae DNA was 73.3% in intact AAA and 10.5% in control aortas, with the highest frequency in ruptured AAA (100%)."

Cheuk / Eur J Vasc Endovasc Surg 2005 abstract / PubMed

Lack of microbial DNA in tissue specimens of patients with abdominal aortic aneurysms and positive Chlamydiales serology. B Falkensammer, C Duftner, R Seiler, M Pavlic, G Walder, D Wilflingseder, H Stoiber, P Klein-Weigel, M Dierich, G Fraedrich, R Würzner, M Schirmer; Innsbruck Abdominal Aortic Aneurysm Trial-Group. Eur J Clin Microbiol Infect Dis 2007 Feb;26(2):141-145. 30 patients and 15 controls were negative for C. pneumoniae.

Falkensammer - Eur J Clin Microbiol Infect Dis 2007 abstract / PubMed

Morphometrical quantification of Chlamydia pneumoniae and Mycoplasma pneumoniae in human atherosclerotic abdominal aortic aneurysms. LJ Pires, PS Gutierrez. Rev Bras Cir Cardiovasc 2007 Sep;22(3):322-331. 10 necropsies of abdominal aneurysmatic aortas, versus 27 controls. By immunoperoxidase staining, "Positive cells for CP were found in all groups, more frequently at the adventitia; no significant difference was detected between the groups (p>0.05). MP was also detected in all groups. This agent predominated in the group of patients with atherosclerosis, but without aneurysms at both tunica intima and adventitia; nevertheless, there were no significant differences between the groups (p>0.05)."

Pires / Rev Bras Cir Cardiovasc 2007 full article

Thoracic aortic aneurysm patients with Chlamydophila pneumoniae infection showed a shift in trace element levels in serum and diseased aortic tissue. C Nyström-Rosander, P Frisk, M Edvinsson, E Hjelm, S Thelin, G Friman, NG Ilbäck. J Trace Elem Med Biol 2009;23(2):100-106. 23 AAA tissue specimens, 10 aortic specimens from forensic autopsy. C. pneumoniae was found in 26% (6/23) of the patients but in none of the controls.

Nyström-Rosander - J Trace Elem Med Biol 2009 abstract / PubMed

Chlamydial lipopolysaccharide (cLPS) is present in atherosclerotic and aneurysmal arterial wall--cLPS levels depend on disease manifestation. P Vikatmaa, T Lajunen, TS Ikonen, PJ Pussinen, M Lepäntalo, M Leinonen, P Saikku. Cardiovasc Pathol 2010 Jan-Feb;19(1):48-54. 50 AAAs, compared to 22 aorto-occlusive disease and 110 carotid artery stenosis. "The median levels of cLPS in plaques were 2.28, 0.80, and 0.29 ng/ml in AAA, aorto-occlusive disease, and carotid artery stenosis patients, respectively (P<.001, Kruskal-Wallis). cLPS in serum correlated with LPS binding protein levels (Spearman's rho=0.52, P<.001), suggesting that the presence of chlamydiae is sufficient to produce an innate immune response reaction in these patients. Serum inflammatory markers interleukin 6 and highly sensitive C-reactive protein also correlate with cLPS (Spearman's rho=0.42 and 0.51, respectively, P<.001)."

Vikatmaa - Cardiovasc Pathol 2010 abstract / PubMed

Quantification and location of Chlamydia pneumoniae-specific antigen in the walls of abdominal aortic aneurysms. F Xiong, JC Zhao. Ann Vasc Surg 2011 Feb;25(2):256-263. 20 patients with AAA and 11 healthy organ donors. By immunohistochemistry, "The positive rate of C pneumoniae-specific antigen was higher in the AAA group than in the control group (100% vs. 54.54%, p = 0.003), positive intensity decreased from the tunica intima to the adventitia in the AAA group (16.32% ± 2.13%, 14.84% ± 1.80%, and 14.25% ± 1.67%, respectively, p = 0.003). In the control group, positive cells were mainly found in focal lesion areas."

Xiong - Ann Vasc Surg 2011 abstract / PubMed

Chlamydia pneumoniae Antibodies and C-Reactive Protein Levels in Patients with Abdominal Aortic Aneurysms. MA Sharif, DA McDowell, SA Badger. ScientificWorld Journal 2013 Dec 28;2013:212450. 250 patients and 250 controls. "196 (78.7%) AAA patients had positive IgA antichlamydial antibody titres, compared to 181 (72.4%) in the control group (P = 0.008, OR 2.0, 95% CI 1.2-3.5). However, positive IgG antibody titres were similar (191 versus 203; P = 0.222, OR 0.7, 95% CI 0.4-1.3). Average CRP concentrations were higher in AAA individuals."

Sharif - ScientificWorldJournal 2013 full article / PubMed Central
Sharif / ScientificWorldJournal 2013 full article

Antibodies to C. pneumoniae phage are important in AAA

Molecular detection and seroepidemiology of the Chlamydia pneumoniae bacteriophage (PhiCpn1). KP Karunakaran, JF Blanchard, A Raudonikiene, C Shen, AD Murdin, RC Brunham. J Clin Microbiol 2002 Nov;40(11):4010-4014. Antibodies to the highly immunogenic viral phage were significantly correlated with AAA (13.9; 1.1-175). 61/72 subjects (32 AAA patients and 40 controls) had C. pneumoniae EB antibodies shown by ELISA. "Antibodies to Vp1 were found in 39 of the 61 (64%) seropositive individuals and were significantly correlated with AAA. Our studies indicate that phage-containing strains of C. pneumoniae are uncommonly found by isolation but may commonly infect individuals with vascular disease."

Karunakaran - J Clin Microbiol 2002 / Full article

Possible pharmacological treatments

Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase. K Yoshimura, H Aoki, Y Ikeda, K Fujii, N Akiyama, A Furutani, Y Hoshii, N Tanaka, R Ricci, T Ishihara, K Esato, K Hamano, M Matsuzaki. Nat Med 2005 Dec;11(12):1330-1338. "Selective inhibition of JNK in vivo not only prevented the development of AAA but also caused regression of established AAA in two mouse models."

Yoshimura - Nat Med 2005 abstract / PubMed

Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms. S Abisi, KG Burnand, J Humphries, M Waltham, P Taylor, A Smith. Br J Surg 2008 Mar;95(3):333-337. "The activities of matrix metalloproteinases (MMPs) 9 and 3, cathepsins B, H, K, L and S, and the cystatin C level were measured in extracts of AAA wall taken from 82 patients undergoing AAA repair; 21 patients were receiving statin treatment before surgery... Cystatin C levels were higher in statin-treated aortas than in controls (41.3(3.1) versus 28.9(2.1) ng per mg SP; P = 0.003)," while activity of proteases that have been implicated in aneurysm disease was lower.

Abisi - Br J Surg 2008 abstract / PubMed

The effect of azithromycin and Chlamydophilia pneumonia infection on expansion of small abdominal aortic aneurysms--a prospective randomized double-blind trial. L Karlsson, J Gnarpe, D Bergqvist, J Lindbäck, H Pärsson. J Vasc Surg 2009 Jul;50(1):23-29. 211 patients with AAA 35-49 mm and age <80 years, randomized to receive either azithromycin or placebo. "Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients... No correlation was found between serological markers for Cpn infection and the expansion rate. Patients taking statins in combination with acetylsalicylic acid (ASA) had significantly reduced expansion rate compared to patients who did not take statins or ASA, 0.14 cm/year vs 0.27 cm/year, P < .001."

Karlsson - J Vasc Surg 2009 abstract / PubMed

Intermittent roxithromycin for preventing progression of small abdominal aortic aneurysms: long-term results of a small clinical trial. A Høgh, S Vammen, L Ostergaard, JB Joensen, EW Henneberg, JS Lindholt. Vasc Endovascular Surg 2009 Oct-Nov;43(5):452-456. "Eighty-four patients with small AAAs were randomized to either an annual 4 weeks' treatment with roxithromycin or placebo, and followed prospectively... Intermittent, long-term Roxithromycin-treatment reduced mean annual growth rate by 36% compared with placebo after adjustment for potential confounders. Long-term roxithromycin-treated patients had a 29% lower risk of being referred for surgical evaluation, increasing to 57% after adjusting for potential confounders."

Høgh - Vasc Endovascular Surg 2009 abstract / PubMed

Possible involvement of cytomegalovirus

High prevalence of circulating CD4+CD28- T-cells in patients with small abdominal aortic aneurysms. C Duftner, R Seiler, P Klein-Weigel, H Gobel, C Goldberger, C Ihling, G Fraedrich, M Schirmer. Arterioscler Thromb Vasc Biol 2005 Jul;25(7):1347-1352. 101 AAA patients and 38 healthy controls. "Both CD4+CD28- and CD8+CD28- T cells produced large amounts of IFN-[gamma] and perforin. Patients with small AAAs (<4 cm) showed higher peripheral levels of CD4+CD28- T cells than those with larger AAAs (P=0.025)."

Duftner - Arterioscler Thromb Vasc Biol 2005 abstract / PubMed

Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection. EM van Leeuwen, EB Remmerswaal, MT Vossen, AT Rowshani, PM Wertheim-van Dillen, RA van Lier, IJ ten Berge. J Immunol 2004 Aug 1;173(3):1834-1841. "In this study, we show that in primary CMV infections, CD4(+)CD28(-) T cells emerge just after cessation of the viral load, indicating that infection with CMV triggers the formation of CD4(+)CD28(-) T cells. In line with this, we found these cells only in CMV-infected persons. CD4(+)CD28(-) cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin. Importantly, CD4(+)CD28(-) cells were to a large extent CMV-specific because proliferation was only induced by CMV-Ag, but not by recall Ags such as purified protein derivative or tetanus toxoid. CD4(+)CD28(-) cells only produced IFN-gamma after stimulation with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to varicella-zoster virus and purified protein derivative. Thus, CD4(+)CD28(-) T cells emerge as a consequence of CMV infection."

van Leeuwen / J Immunol 2004 full article

Active cytomegalovirus infection in aortic smooth muscle cells from patients with abdominal aortic aneurysm. S Gredmark-Russ, M Dzabic, A Rahbar, A Wanhainen, M Björck, E Larsson, JB Michel, C Söderberg-Nauclér. J Mol Med 2009 Apr;87(4):347-356. "Twenty-one (95%) of the 22 AAA specimens were CMV positive by a polymerase chain reaction assay, in situ hybridization, or a highly sensitive immunohistochemical staining technique. No positive cells were found in aortas from three CMV-seronegative organ donor cadavers."

Gredmark-Russ - J Mol Med 2009 abstract / PubMed

Other bacteria / mechanisms

Bacterial diversity in aortic aneurysms determined by 16S ribosomal RNA gene analysis. R Marques da Silva, DA Caugant, ER Eribe, JA Aas, PA Lingaas, O Geiran, L Tronstad, I Olsen. J Vasc Surg 2006 Nov;44(5):1055-1060. In 10 specimens from arterial walls of aortic aneurysms, numerous strains of bacteria were found, including skin, oral and gastrointestinal types.

Marques da Silva - J Vasc Surg 2006 abstract / PubMed

Cysteine protease activity in the wall of abdominal aortic aneurysms. S Abisi, KG Burnand, M Waltham, J Humphries, PR Taylor, A Smith. J Vasc Surg 2007 Dec;46(6):1260-1266. Comparison of aortic wall samples from 82 patients with AAA and 13 with AOD (aortic occlusive disease). "The activity of four cathepsins B, H, L, and S was higher in the aneurysm wall than in aortic wall of patients with occlusive disease. This was associated with a reduced level of cystatin C in the aneurysmal wall."

Abisi - J Vasc Surg 2007 abstract / PubMed

Cathepsin B, K, and S are expressed in cerebral aneurysms and promote the progression of cerebral aneurysms. T Aoki, H Kataoka, R Ishibashi, K Nozaki, N Hashimoto. Stroke 2008 Sep;39(9):2603-2610. In rats, "Quantitative RT-PCR and immunohistochemistry revealed upregulated expression of cathepsin B, K, and S in the late stage of aneurysm progression. In contrast, cystatin C expression was reduced with aneurysm progression. Treatment with NC-2300 resulted in the decreased incidence of advanced CAs." The same expression pattern was found in human cerebral aneurysms.

Aoki . Stroke 2008 abstract / PubMed

P. gingivalis regulates the expression of Cathepsin B and Cystatin C.R Elkaim, S Werner, L Kocgozlu, H Tenenbaum. J Dent Res 2008 Oct;87(10):932-936. "Porphyromonas gingivalis is a major etiological agent of periodontitis that could affect the expression of Cathepsins B and C by disrupting the balance between these enzymes and their inhibitor, Cystatin C. We tested this hypothesis by infecting human oral epithelial cells with P. gingivalis or activating solely by its lipopolysaccharide. The mRNA level, the enzymatic activity, and the protein expression of Cathepsin B were increased (three-fold) in a dose-dependent manner, while those of Cystatin C decreased (five-fold). No changes were observed for Cathepsin C. Although activation by lipopolysaccharides led to a delayed imbalance (2 days) between Cathepsin B and Cystatin C, this imbalance took place very rapidly during the infection (< 6 hrs), indicating that the whole bacterium contains components that initiate rapid changes in the transcription rates of Cathepsin B and Cystatin C and selectively modify the molecular pathways that lead to this imbalance."

Elkaim - J Dent Res 2008 abstract / PubMed

Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis. Z Armingohar, JJ Jørgensen, AK Kristoffersen, E Abesha-Belay, I Olsen. J Oral Microbiol 2014 May 15;6. 27 biopsies from abdominal aortic aneurysmal walls, 9 from carotid, and 4 from common femoral atherosclerotic plaque. "A higher load and mean diversity of bacteria were detected in vascular biopsies from VD patients with CP compared to those without CP. Enterobacteriaceae were frequently detected in vascular biopsies together with cultivable, commensal oral, and not-yet-cultured bacterial species. While 70% of the subgingival plaque samples from CP patients showed presence of RCB, only P. gingivalis was detected in one vascular biopsy. Bacterial cells were seen in all 10 vascular biopsies examined by SEM."

Armingohar - J Oral Microbiol 2014 full article / PubMed Central


The prevalence of abdominal aortic aneurysm is consistently high among patients with coronary artery disease. JA Hernesniemi, V Vänni, T Hakala. J Vasc Surg 2015 Jul;62(1):232-240. "Among the general population, 23 studies reported the association between CHD and the occurrence of subclinical AAA (positive ultrasound screening; meta-analyzed odds ratio of 2.38 with 95% confidence interval [CI] of 1.78-3.19; P = 4.1 × 10(-9)). According to four prospective studies, CHD is a strong predictor of future AAA events (fatal and nonfatal; meta-analyzed hazard ratio of 3.49 with 95% CI of 2.56-4.76; P = 2.4 × 10(-15)). Altogether, 10 studies reported the prevalence of AAA among patients with angiography-verified CAD or undergoing coronary artery bypass grafting. Among men, meta-analyzed prevalence was 9.5% (95% CI, 7.6%-11.7%). Among men undergoing coronary artery bypass grafting or with three-vessel disease, the prevalence was 11.4% (95% CI, 9.1%-13.9%). Among women, the prevalence was low (0.35%)."

Hernesniemi - J Vasc Surg 2015 abstract / PubMed

See also:

Chlamydia pneumoniae causes heart disease
Abdominal Aortic Aneurism /


cast 06-28-15