Involvement of Chlamydia pneumoniae in Atherosclerosis: More Evidence for Lack of Evidence

Abstract

During the past 15 years, many studies have been devoted to the relationship of Chlamydia pneumoniae and atherosclerosis: the serologic link has been investigated, and chlamydial organisms have been detected in lesions by electron microscopy, immunohistochemistry, in vitro cultivation, PCR, or in situ hybridization; efforts have been made to produce atherosclerosis experimentally in animals by inoculation of C. pneumoniae and therapeutic trials in humans have been undertaken. Some studies conclude that C. pneumoniae is present in cases of atherosclerosis, while others deny this, splitting the medical community into believers and disbelievers. The question, being a scientific one, should be resolved on a rational basis. After Boman and Hammerschlag reviewed the problem in 2002 (Clin. Microbiol. Rev. 15:1-20, 2002), a number of new studies were published on the subject. In this review, we critically evaluate the available data for the evidence or lack of evidence of a causal relationship for C. pneumoniae in atherosclerosis based on diagnostic and therapeutic studies performed with humans between 1992 and 2003, thereby searching mainly for concordance of evidence arising from different approaches used by different groups, at different times, and under different circumstances. In 1988, Saikku et al. (61) reported that patients with coronary artery disease carry significantly more anti-Chlamydia pneumoniae immunoglobulin G (IgG) and IgA antibodies in their bloodstream than healthy controls. Since this initial study, a huge number of cross-sectional and case-control studies addressing the involvement of C. pneumoniae in atherosclerosis have been published. Several, but not all, of these studies found a similar positive association. Prospective studies, in which results were generally adjusted for the presence of traditional risk factors, seem to minimize the relationship between baseline C. pneumoniae IgG titers in the healthy population and the risk for a subsequent coronary event. Furthermore, the presence of elevated anti-C. pneumoniae antibodies in patients with preexisting vascular disease means no increased risk for future or recurrent cardiovascular events. SEROEPIDEMIOLOGIC STUDIESThis serologic link between C. pneumoniae and vascular diseases has been studied by the microimmunofluorescence (MIF) test and enzyme-linked immunosorbent assays (ELISAs). There is, however, accumulating evidence that Chlamydia serology is less specific than was first assumed. Cross-reactivity between C. pneumoniae and other Chlamydia species has been demonstrated with the MIF test. In addition, neither the serologic procedures nor the criteria for defining an infection with C. pneumoniae are standardized. A standardization workshop held in 2001 (18) recommended that the MIF test should be considered the only acceptable serologic test for Chlamydia and that an IgG titer of Ն1/16 indicates past exposure but that neither elevated IgA titers nor any other serologic marker may be used as a validated indicator of persistent or chronic ...

GroEL1, a Heat Shock Protein 60 of Chlamydia pneumoniae, Induces Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Expression in Endothelial Cells and Enhances Atherogenesis in Hypercholesterolemic Rabbits

“…The role of C. pneumoniae infection in the pathogenesis of atherosclerosis remains controversial (21)(22)(23)(24). Meta-analyses of randomized clinical trials of antibiotic therapy for secondary prevention of coronary heart disease did not show any benefit (25, 26).…”

Detección de Chlamydia pneumoniae en tejido aórtico humano: amplificación del gen kdtA e hibridación in vitro.

“…Este es un valor elevado si se lo compara con estudios revisados en los últimos 5 años (15,(22)(23)(24)(25)(26). No obstante, en un estudio reciente, Bahrmand et al (6) demostraron que 12 de 14 (86%) casos eran positivos para C. pneumoniae por PCR en pacientes de 60 años o mayores.…”

“…La evidencia de una relación entre Chlamydia pneumoniae y la enfermedad coronaria es mucho más concluyente que para cualquier otro de los microorganismos posiblemente implicados (2,6,7,14), y se ha asociado con la presencia de enfermedad coronaria, carotídea, aneurismas de aorta y enfermedad vascular periférica (7). No obstante, otros reportes no confirman dicha asociación (15).…”

“…Los dos tipos de metodología presentan algunas limitaciones, y los reportes de las tasas de detección varían en diferentes publicaciones (15), lo cual evidencia la necesidad de explorar otros protocolos para detectar la presencia del microorganismo en el tejido vascular (18). La evidencia más fehaciente de la asociación existente entre la enfermedad y la infección por C. pneumoniae se ha establecido mediante el uso de la reacción en cadena de la polimerasa (PCR), técnica que ha permitido detectar la presencia de ADN de C. pneumoniae directamente en las placas ateromatosas (7).…”

Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells

“…Current studies indicate that this organism may also induce chronic inflammatory diseases such as asthma, arthritis, endocarditis and atherosclerosis [4][5][6][7]. Although accumulating studies have indicated a possible link between C. pneumoniae infection and chronic inflammatory diseases, the bacterial mechanisms involved in disease development remain unclear [8]. In addition to macrophages, lymphocytes are the major immune cell associated with the development of chronic inflammatory diseases, such as atherosclerosis [9,10].…”