Persistent Chlamydia pneumoniae infection of cardiomyocytes is correlated with fatal myocardial infarction.

Acute myocardial infarction (AMI) associated with unfavorable prognosis is likely to be the consequence of a diffuse active chronic inflammatory process that destabilizes the whole coronary tree and myocardium, suggesting a possible common causal agent underlying both conditions. The main objective of this study was to investigate whether Chlamydia pneumoniae (CP) infection occurred beyond the coronary plaques, namely in the myocardium of individuals who died of AMI. The presence of CP cell wall antigen (OMP-2) and CP-HSP60 was investigated in the myocardium and coronary plaques of 10 AMI and 10 age-matched control patients by immunohistochemistry, electron microscopy, and molecular biology. OMP-2 antigens were found in the unaffected myocardium of 9 of 10 AMI patients. Conversely, only 1 of 10 control patients exhibited a positive staining for CP. Moreover, OMP-2 and CP-HSP60 were detected in the whole coronary tree. CP presence was strongly associated with a T-cell inflammatory infiltrate. Our results suggest that CP may underlie both coronary and myocardial vulnerabilities in patients who died of AMI and corroborate the notion that CP may act by reducing cardiac reserves, thus worsening the ischemic burden of myocardium.

[1]  I. Vliegen,et al.  Immune activation following cytomegalovirus infection: more important than direct viral effects in cardiovascular disease? , 2006, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[2]  Alexander Reinecke,et al.  Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease , 2006, Circulation.

[3]  J. Katz,et al.  Bacteria and coronary atheroma: more fingerprints but no smoking gun. , 2006, Circulation.

[4]  H. Schultheiss,et al.  Viral Persistence in the Myocardium Is Associated With Progressive Cardiac Dysfunction , 2005, Circulation.

[5]  P. Libby.  Act local, act global: inflammation and the multiplicity of "vulnerable" coronary plaques. , 2005, Journal of the American College of Cardiology.

[6]  Elena Bonanno,et al.  Diffuse and active inflammation occurs in both vulnerable and stable plaques of the entire coronary tree: a histopathologic study of patients dying of acute myocardial infarction. , 2005, Journal of the American College of Cardiology.

[7]  M. D’Elios,et al.  Human 60-kDa Heat Shock Protein Is a Target Autoantigen of T Cells Derived from Atherosclerotic Plaques 1 , 2005, The Journal of Immunology.

[8]  R. Kronmal,et al.  Azithromycin for the secondary prevention of coronary events. , 2005, The New England journal of medicine.

[9]  Jeffrey L. Anderson.  Infection, antibiotics, and atherothrombosis--end of the road or new beginnings? , 2005, The New England journal of medicine.

[10]  A. Skene,et al.  Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome. , 2005, The New England journal of medicine.

[11]  Frank J Giordano,et al.  Oxygen, oxidative stress, hypoxia, and heart failure. , 2005, The Journal of clinical investigation.

[12]  A. M. Leone,et al.  Widespread Myocardial Inflammation and Infarct-Related Artery Patency , 2004, Circulation.

[13]  E. Boerwinkle,et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. , 2003, Circulation.

[14]  F. Crea,et al.  Antibody Response to Chlamydial Heat Shock Protein 60 Is Strongly Associated With Acute Coronary Syndromes , 2003, Circulation.

[15]  M. D’Elios,et al.  T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Peter Libby,et al.  Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. , 2002, JAMA.

[17]  G. Zhong,et al.  Infection of myocytes with chlamydiae. , 2002, Microbiology.

[18]  F. Crea,et al.  Multicentric inflammation in epicardial coronary arteries of patients dying of acute myocardial infarction. , 2002, Journal of the American College of Cardiology.

[19]  M. Hammerschlag.  The intracellular life of chlamydiae. , 2002, Seminars in pediatric infectious diseases.

[20]  P. Visca,et al.  Antibodies to 60-Kilodalton Heat Shock Protein and Outer Membrane Protein 2 of Chlamydia pneumoniae in Patients with Coronary Heart Disease , 2002, Clinical and Vaccine Immunology.

[21]  M. Hammerschlag,et al.  Chlamydia pneumoniae and Atherosclerosis: Critical Assessment of Diagnostic Methods and Relevance to Treatment Studies , 2002, Clinical Microbiology Reviews.

[22]  F. Lauro,et al.  Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions. , 2001, Atherosclerosis.

[23]  H. Katus,et al.  Chlamydia pneumoniae Infection in Circulating Human Monocytes Is Refractory to Antibiotic Treatment , 2001, Circulation.

[24]  J. Tu,et al.  Rate of heart failure and 1-year survival for older people receiving low-dose β-blocker therapy after myocardial infarction , 2000, The Lancet.

[25]  J. Penninger,et al.  Review of microbial infections and the immune response to cardiac antigens. , 2000, The Journal of infectious diseases.

[26]  R. Virmani,et al.  Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[27]  T. Hackstadt,et al.  Ultrastructural Analysis of Developmental Events inChlamydia pneumoniae-Infected Cells , 2000, Infection and Immunity.

[28]  T. Quinn,et al.  Touchdown Enzyme Time Release-PCR for Detection and Identification of Chlamydia trachomatis, C. pneumoniae, and C. psittaci Using the 16S and 16S-23S Spacer rRNA Genes , 2000, Journal of Clinical Microbiology.

[29]  A. Becker,et al.  Atherosclerosis, inflammation, and infection , 2000, The Journal of pathology.

[30]  M. Mayr,et al.  Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of Escherichia coli and Chlamydia pneumoniae: immune reactions to heat shock proteins as a possible link between infection and atherosclerosis. , 1999, Circulation.

[31]  J. Penninger,et al.  Chlamydia infections and heart disease linked through antigenic mimicry. , 1999, Science.

[32]  P. Libby,et al.  Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. , 1999, The Journal of clinical investigation.

[33]  K. Dalhoff,et al.  Interaction of Chlamydia pneumoniae and human alveolar macrophages: infection and inflammatory response. , 1998, American journal of respiratory cell and molecular biology.

[34]  M. Zembala,et al.  Immunohistological diagnosis of myocarditis. Potential role of sarcolemmal induction of the MHC and ICAM-1 in the detection of autoimmune mediated myocyte injury. , 1998, European heart journal.

[35]  P. Libby,et al.  Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression. , 1998, Circulation.

[36]  J. Danesh,et al.  Risk factors for coronary heart disease and infection with Helicobacter pylori: meta-analysis of 18 studies , 1998, BMJ.

[37]  J. Danesh,et al.  Chronic infections and coronary heart disease: is there a link? , 1997, The Lancet.

[38]  A. Lee,et al.  Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. , 1997, The Journal of infectious diseases.

[39]  G. Rodgers,et al.  Chlamydia species infect human vascular endothelial cells and induce procoagulant activity. , 1997, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[40]  J. Ramirez,et al.  Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells , 1996, Infection and immunity.

[41]  J. Witztum,et al.  T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[42]  H. Fukushi,et al.  Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. , 1993, The Journal of infectious diseases.

[43]  K. Sell,et al.  Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis. , 1990, Journal of the American College of Cardiology.

[44]  M. Nieminen,et al.  SEROLOGICAL EVIDENCE OF AN ASSOCIATION OF A NOVEL CHLAMYDIA, TWAR, WITH CHRONIC CORONARY HEART DISEASE AND ACUTE MYOCARDIAL INFARCTION , 1988, The Lancet.

[45]  B. Lüderitz,et al.  Persistence of Chlamydia pneumoniae in degenerative aortic valve stenosis indicated by heat shock protein 60 homologues. , 2003, The Journal of heart valve disease.

[46]  G. Pasterkamp,et al.  Multiple complex coronary plaques in patients with acute myocardial infarction. , 2001, The New England journal of medicine.