Pathogens and atherosclerosis: Update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis

Summary

It is currently unclear what causes the chronic inflammation within atherosclerotic plaques. One emerging paradigm suggests that infection with bacteria and/or viruses can contribute to the pathogenesis of atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at non-vascular sites. This paradigm has been supported by multiple epidemiological studies that have established positive associations between the risk of cardiovascular disease morbidity and mortality and markers of infection. It has also been supported by experimental studies showing an acceleration of the development of atherosclerosis following infection of hyperlipidaemic animal models. There are now a large number of different infectious agents that have been linked with an increased risk of cardiovascular disease. These include: Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori, influenza A virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. However, there are significant differences in the strength of the data supporting their association with cardiovascular disease pathogenesis. In some cases, the infectious agents are found within the plaques and viable organisms can be isolated suggesting a direct effect. In other cases, the association is entirely based on biomarkers. In the following review, we evaluate the strength of the data for individual or groups of pathogens with regard to atherosclerosis pathogenesis and their potential contribution by direct or indirect mechanisms and discuss whether the established associations are supportive of the infectious disease paradigm. We also discuss the failure of antibiotic trials and the question of persistent infection.

Keywords

Atherosclerosis - bacterial infection - inflammation - infectious diseases

• References

• 1 Fabricant CG. et al. Virus-induced atherosclerosis. J Exp Med 1978; 148: 335-340.
• 2 Shor A. et al. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J 1992; 82: 158-161.
• 3 Grayston JT. et al. Chlamydia pneumoniae, strain TWAR and atherosclerosis. Eur Heart J 1993; 14: 66-71. Suppl K
• 4 Jiang B. et al. HIV-1 antiretrovirals induce oxidant injury and increase intima-media thickness in an atherogenic mouse model. Toxicol Lett 2009; 187: 164-171.
• 5 Ford P. et al. Characterization of heat shock protein-specific T cells in atherosclerosis. Clin Diagn Lab Immunol 2005; 12: 259-267.
• 6 Binder CJ. et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med 2003; 9: 736-743.
• 7 Lamb DJ. et al. Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Atherosclerosis 2003; 167: 177-185.
• 8 Epstein SE. et al. Infection and atherosclerosis: potential roles of pathogen burden and molecular mimicry. Arterioscler Thromb Vasc Biol 2000; 20: 1417-1420.
• 9 Elkind MS. et al. Infectious burden and carotid plaque thickness: the northern Manhattan study. Stroke 2010; 41: e117-122.
• 10 Zhu J. et al. Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels. Am J Cardiol 2000; 85: 140-146.
• 11 Belland RJ. et al. Chlamydia pneumoniae and atherosclerosis. Cell Microbiol 2004; 6: 117-127.
• 12 Berger M. et al. Chlamydia pneumoniae DNA in non-coronary atherosclerotic plaques and circulating leukocytes. J Lab Clin Med 2000; 136: 194-200.
• 13 Ramirez JA. Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. The Chlamydia pneumoniae/Atherosclerosis Study Group. Ann Intern Med 1996; 125: 979-982.
• 14 Jackson LA. et al. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis 1997; 176: 292-295.
• 15 Mosorin M. et al. Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery. Arterioscler Thromb Vasc Biol 2000; 20: 1061-1067.
• 16 Benagiano M. et al. Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques. J Immunol 2005; 174: 6509-6517.
• 17 Moazed TC. et al. Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis 1999; 180: 238-241.
• 18 Blessing E. et al. Chlamydia pneumoniae infection accelerates hyperlipidemia induced atherosclerotic lesion development in C57BL/6J mice. Atherosclerosis 2001; 158: 13-17.
• 19 Burnett MS. et al. Atherosclerosis in apoE knockout mice infected with multiple pathogens. J Infect Dis 2001; 183: 226-231.
• 20 Ezzahiri R. et al. Chlamydophila pneumoniae (Chlamydia pneumoniae) accelerates the formation of complex atherosclerotic lesions in Apo E3-Leiden mice. Cardiovasc Res 2002; 56: 269-276.
• 21 Fong IW. et al. Rabbit model for Chlamydia pneumoniae infection. J Clin Microbiol 1997; 35: 48-52.
• 22 Herrera VL. et al. Chlamydia pneumoniae accelerates coronary artery disease progression in transgenic hyperlipidemia-genetic hypertension rat model. Mol Med 2003; 9: 135-142.
• 23 Hu H. et al. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest 1999; 103: 747-753.
• 24 Laitinen K. et al. Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits. Infect Immun 1997; 65: 4832-4835.
• 25 Liu L. et al. Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR-/- mouse model within six months. Mol Cell Biochem 2000; 215: 123-128.
• 26 Muhlestein JB. et al. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 1998; 97: 633-636.
• 27 Rothstein NM. et al. Effect of azithromycin on murine arteriosclerosis exacerbated by Chlamydia pneumoniae. J Infect Dis 2001; 183: 232-238.
• 28 Erkkila L. et al. Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection. Atherosclerosis 2004; 177: 321-328.
• 29 Caligiuri G. et al. Chlamydia pneumoniae infection does not induce or modify atherosclerosis in mice. Circulation 2001; 103: 2834-2838.
• 30 Aalto-Setala K. et al. Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2001; 21: 578-584.
• 31 Campbell LA. et al. Tumor necrosis factor alpha plays a role in the acceleration of atherosclerosis by Chlamydia pneumoniae in mice. Infect Immun 2005; 73: 3164-3165.
• 32 Chen S. et al. IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice. J Immunol 2010; 185: 5619-5627.
• 33 Campbell LA. et al. The acute phase reactant response to respiratory infection with Chlamydia pneumoniae: implications for the pathogenesis of atherosclerosis. Microbes Infect 2010; 12: 598-606.
• 34 Naiki Y. et al. TLR/MyD88 and liver X receptor alpha signaling pathways reciprocally control Chlamydia pneumoniae-induced acceleration of atherosclerosis. J Immunol 2008; 181: 7176-7185.
• 35 Ezzahiri R. et al. Chlamydia pneumoniae infections augment atherosclerotic lesion formation: a role for serum amyloid P. APMIS 2006; 114: 117-126.
• 36 Chen S. et al. Chlamydia pneumoniae-induced foam cell formation requires MyD88-dependent and -independent signaling and is reciprocally modulated by liver X receptor activation. J Immunol 2008; 181: 7186-7193.
• 37 Trevisan M, Dorn J. The relationship between periodontal disease (pd) and cardiovascular disease (cvd). Mediterr J Hematol Infect Dis 2010; 2: e2010030
• 38 Beck JD, Offenbacher S. Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease. J Periodontol 2005; 76: 2089-2100. (Suppl. 11) Suppl
• 39 Chiu B. Multiple infections in carotid atherosclerotic plaques. Am Heart J 1999; 138: S534-536.
• 40 Ford PJ. et al. Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study. Oral Microbiol Immunol 2006; 21: 206-211.
• 41 Haraszthy VI. et al. Identification of periodontal pathogens in atheromatous plaques. J Periodontol 2000; 71: 1554-1560.
• 42 Padilla C. et al. Periodontal pathogens in atheromatous plaques isolated from patients with chronic periodontitis. J Periodontal Res 2006; 41: 350-353.
• 43 Nakano K. et al. Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens. J Clin Microbiol 2006; 44: 3313-3317.
• 44 Kozarov E. et al. Detection of bacterial DNA in atheromatous plaques by quantitative PCR. Microbes Infect 2006; 8: 687-693.
• 45 Aquino AR. et al. Molecular survey of atheromatous plaques for the presence of DNA from periodontal bacterial pathogens, archaea and fungi. J Periodontal Res 2011; 46: 305-309.
• 46 Fiehn NE. et al. Identification of periodontal pathogens in atherosclerotic vessels. J Periodontol. 2005; 76: 731-736.
• 47 Teles R, Wang CY. Mechanisms involved in the association between peridontal diseases and cardiovascular disease. Oral Dis 2011; 17: 450-461.
• 48 Glurich I. et al. Systemic inflammation in cardiovascular and periodontal disease: comparative study. Clin Diagn Lab Immunol 2002; 9: 425-432.
• 49 Buhlin K. et al. Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis. Atherosclerosis 2009; 206: 518-522.
• 50 Lalla E. et al. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 2003; 23: 1405-1411.
• 51 Madan M. et al. Doxycycline affects diet- and bacteria-associated atherosclerosis in an ApoE heterozygote murine model: cytokine profiling implications. Atherosclerosis 2007; 190: 62-72.
• 52 Champagne C. et al. Gender differences in systemic inflammation and atheroma formation following Porphyromonas gingivalis infection in heterozygous apolipoprotein E-deficient mice. J Periodontal Res 2009; 44: 569-577.
• 53 Amar S. et al. Is Porphyromonas gingivalis cell invasion required for atherogenesis? Pharmacotherapeutic implications. J Immunol 2009; 182: 1584-1592.
• 54 Ford PJ. et al. Anti-P. gingivalis response correlates with atherosclerosis. J Dent Res 2007; 86: 35-40.
• 55 Koizumi Y. et al. Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P. gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice. Infect Immun 2008; 76: 2958-2965.
• 56 Gitlin JM, Loftin CD. Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice. Cardiovasc Res 2009; 81: 400-407.
• 57 Hayashi C. et al. Pathogen-mediated inflammatory atherosclerosis is mediated in part via Toll-like receptor 2-induced inflammatory responses. J Innate Immun 2010; 2: 334-343.
• 58 Hayashi C. et al. Porphyromonas gingivalis accelerates inflammatory atherosclerosis in the innominate artery of ApoE deficient mice. Atherosclerosis 2011; 215: 52-59.
• 59 Li L. et al. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation 2002; 105: 861-867.
• 60 Miyamoto T. et al. Pathogen-accelerated atherosclerosis occurs early after exposure and can be prevented via immunization. Infect Immun 2006; 74: 1376-1380.
• 61 Tuomainen AM. et al. Aggregatibacter actinomycetemcomitans induces MMP-9 expression and proatherogenic lipoprotein profile in apoE-deficient mice. Microb Pathog 2008; 44: 111-117.
• 62 Zhang T. et al. Aggregatibacter actinomycetemcomitans accelerates atherosclerosis with an increase in atherogenic factors in spontaneously hyperlipidemic mice. FEMS Immunol Med Microbiol 2010; 59: 143-151.
• 63 Giacona MB. et al. Porphyromonas gingivalis induces its uptake by human macrophages and promotes foam cell formation in vitro. FEMS Microbiol Lett 2004; 241: 95-101.
• 64 Griffiths R, Barbour S. Lipoproteins and lipoprotein metabolism in periodontal disease. Clin Lipidol 2010; 5: 397-411.
• 65 Adiloglu AK. et al. Detection of Helicobacter pylori and Chlamydia pneumoniae DNA in human coronary arteries and evaluation of the results with serologic evidence of inflammation. Saudi Med J 2005; 26: 1068-1074.
• 66 Ameriso SF. et al. Detection of Helicobacter pylori in human carotid atherosclerotic plaques. Stroke 2001; 32: 385-391.
• 67 Ghirardi G. et al. Helicobacter pylori detected in atheroma plaque. Rev Fac Cien Med Univ Nac Cordoba 2006; 63: 17-23.
• 68 Kaplan M. et al. Detection of Chlamydia pneumoniae and Helicobacter pylori in atherosclerotic plaques of carotid artery by polymerase chain reaction. Int J Infect Dis 2006; 10: 116-123.
• 69 Kowalski M. Helicobacter pylori (H. pylori) infection in coronary artery disease: influence of H. pylori eradication on coronary artery lumen after percutaneous transluminal coronary angioplasty. The detection of H. pylori specific DNA in human coronary atherosclerotic plaque. J Physiol Pharmacol 2001; 52: 3-31. (Suppl. 01) Suppl
• 70 Latsios G. et al. Detection of cytomegalovirus, Helicobacter pylori and Chlamydia pneumoniae DNA in carotid atherosclerotic plaques by the polymerase chain reaction. Acta Cardiol 2004; 59: 652-657.
• 71 Reszka E. et al. Detection of infectious agents by polymerase chain reaction in human aortic wall. Cardiovasc Pathol 2008; 17: 297-302.
• 72 Brenner H. et al. Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults: results from a large population-based study. Atherosclerosis 1999; 147: 399-403.
• 73 Elizalde JI. et al. Effects of Helicobacter pylori eradication on platelet activation and disease recurrence in patients with acute coronary syndromes. Helicobacter 2004; 9: 681-689.
• 74 Stone AF. et al. Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA). Circulation 2002; 106: 1219-1223.
• 75 Schweeger I. et al. Successful eradication of Helicobacter pylori as determined by ((13))C-urea breath test does not alter fibrinogen and acute phase response markers. Thromb Res 2000; 97: 411-420.
• 76 Chen XH. et al. Helicobacter pylori infection enhances atherosclerosis in high-cholesterol diet fed C57BL/6 mice. Zhonghua Xin Xue Guan Bing Za Zhi 2010; 38: 259-263.
• 77 Mach F. et al. Influence of Helicobacter pylori infection during atherogenesis in vivo in mice. Circ Res 2002; 90: E1-4.
• 78 Ayada K. et al. Chronic infections and atherosclerosis. Ann NY Acad Sci 2007; 1108: 594-602.
• 79 Ayada K. et al. Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis. Lupus 2009; 18: 1154-1168.
• 80 Weiss TW. et al. No evidence for a direct role of Helicobacter pylori and Mycoplasma pneumoniae in carotid artery atherosclerosis. J Clin Pathol 2006; 59: 1186-1190.
• 81 Rafferty B. et al. Cultivation of Enterobacter hormaechei from human atherosclerotic tissue. J Atheroscler Thromb 2011; 18: 72-81.
• 82 Volzke H. et al. Seropositivity for anti-Borrelia IgG antibody is independently associated with carotid atherosclerosis. Atherosclerosis 2006; 184: 108-112.
• 83 Fateh-Moghadam S. et al. Cytomegalovirus infection status predicts progression of heart-transplant vasculopathy. Transplantation 2003; 76: 1470-1474.
• 84 Grattan MT. et al. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. J Am Med Assoc 1989; 261: 3561-3566.
• 85 Roberts ET. et al. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol 2010; 172: 363-371.
• 86 Melnick JL. et al. Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J Med Virol 1994; 42: 170-174.
• 87 Horvath R. et al. The possible role of human cytomegalovirus (HCMV) in the origin of atherosclerosis. J Clin Virol 2000; 16: 17-24.
• 88 Menschikowski M. et al. Expression of secretory group IIA phospholipase A(2) in relation to the presence of microbial agents, macrophage infiltrates, and transcripts of proinflammatory cytokines in human aortic tissues. Arterioscler Thromb Vasc Biol 2000; 20: 751-762.
• 89 Radke PW. et al. Infectious agents in coronary lesions obtained by endatherectomy: pattern of distribution, coinfection, and clinical findings. Coron Artery Dis 2001; 12: 1-6.
• 90 Andrie R. et al. Prevalence of intimal pathogen burden in acute coronary syndromes. Z Kardiol 2003; 92: 641-649.
• 91 Chen R. et al. The relationship between human cytomegalovirus infection and atherosclerosis development. Mol Cell Biochem 2003; 249: 91-96.
• 92 Lin TM. et al. Increased incidence of cytomegalovirus but not Chlamydia pneumoniae in atherosclerotic lesions of arteries of lower extremities from patients with diabetes mellitus undergoing amputation. J Clin Pathol 2003; 56: 429-432.
• 93 Kwon TW. et al. Detection of enterovirus, cytomegalovirus, and Chlamydia pneumoniae in atheromas. J Microbiol 2004; 42: 299-304.
• 94 Ibrahim AI. et al. Detection of herpes simplex virus, cytomegalovirus and Epstein-Barr virus DNA in atherosclerotic plaques and in unaffected bypass grafts. J Clin Virol 2005; 32: 29-32.
• 95 Liu R. et al. Presence and severity of Chlamydia pneumoniae and Cytomegalovirus infection in coronary plaques are associated with acute coronary syndromes. Int Heart J 2006; 47: 511-519.
• 96 Virok D. et al. Chlamydophila pneumoniae and human cytomegalovirus in atherosclerotic carotid plaques--combined presence and possible interactions. Acta Microbiol Immunol Hung 2006; 53: 35-50.
• 97 Pucar A. et al. Correlation between atherosclerosis and periodontal putative pathogenic bacterial infections in coronary and internal mammary arteries. J Periodontol 2007; 78: 677-682.
• 98 Kraml PJ. et al. Markers of Chlamydia pneumoniae and human cytomegalovirus infection in patients with chronic peripheral vascular disease and their relation to inflammation, endothelial dysfunction and changes in lipid metabolism. Folia Microbiol (Praha) 2008; 53: 551-557.
• 99 Jha HC. et al. Prevalence of Chlamydophila pneumoniae is higher in aorta and coronary artery than in carotid artery of coronary artery disease patients. APMIS 2009; 117: 905-911.
• 100 Bartels C. et al. Detection of Chlamydia pneumoniae but not cytomegalovirus in occluded saphenous vein coronary artery bypass grafts. Circulation 1999; 99: 879-882.
• 101 Benditt EP. et al. Viruses in the etiology of atherosclerosis. Proc Natl Acad Sci USA 1983; 80: 6386-6389.
• 102 Ciervo A. et al. Real-time polymerase chain reaction and laser capture microdissection: an efficient combination tool for Chlamydophila pneumoniae DNA quantification and localization of infection in atherosclerotic lesions. Int J Immunopathol Pharmacol 2008; 21: 421-428.
• 103 Daus H. et al. Lack of evidence for a pathogenic role of Chlamydia pneumoniae and cytomegalovirus infection in coronary atheroma formation. Cardiology 1998; 90: 83-88.
• 104 Hagiwara N. et al. Lack of association between infectious burden and carotid atherosclerosis in Japanese patients. J Stroke Cerebrovasc Dis 2007; 16: 145-152.
• 105 Muller BT. et al. Chlamydia pneumoniae, herpes simplex virus and cytomegalovirus in symptomatic and asymptomatic high-grade internal carotid artery stenosis. Does infection influence plaque stability?. Vasa 2005; 34: 163-169.
• 106 Saetta A. et al. Atherosclerosis of the carotid artery: absence of evidence for CMV involvement in atheroma formation. Cardiovasc Pathol 2000; 9: 181-183.
• 107 Sambiase NV. et al. CMV and transplant-related coronary atherosclerosis: an immunohistochemical, in situ hybridization, and polymerase chain reaction in situ study. Mod Pathol 2000; 13: 173-179.
• 108 Hsich E. et al. Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice. Atherosclerosis 2001; 156: 23-28.
• 109 Vliegen I. et al. Cytomegalovirus infection aggravates atherogenesis in apoE knockout mice by both local and systemic immune activation. Microbes Infect 2004; 6: 17-24.
• 110 Vliegen I. et al. Mouse cytomegalovirus antigenic immune stimulation is sufficient to aggravate atherosclerosis in hypercholesterolemic mice. Atherosclerosis 2005; 181: 39-44.
• 111 Vliegen I. et al. MCMV infection increases early T-lymphocyte influx in atherosclerotic lesions in apoE knockout mice. J Clin Virol 2002; 25 Suppl S159-171. (Suppl. 02)
• 112 Vliegen I. et al. Murine cytomegalovirus infection directs macrophage differentiation into a pro-inflammatory immune phenotype: implications for atherogenesis. Microbes Infect 2004; 6: 1056-1062.
• 113 Cheng J. et al. Cytomegalovirus infection causes an increase of arterial blood pressure. PLoS Pathog 2009; 5: e1000427
• 114 Zhu J. et al. The possible role of hepatitis A virus in the pathogenesis of atherosclerosis. J Infect Dis 2000; 182: 1583-1587.
• 115 Alyan O. et al. Hepatitis C infection is associated with increased coronary artery atherosclerosis defined by modified Reardon severity score system. Circ J 2008; 72: 1960-1965.
• 116 Ishizaka N. et al. Increased prevalence of carotid atherosclerosis in hepatitis B virus carriers. Circulation 2002; 105: 1028-1030.
• 117 Ishizaka Y. et al. Association between hepatitis C virus core protein and carotid atherosclerosis. Circ J 2003; 67: 26-30.
• 118 Nikolopoulou A. et al. Common community infections and the risk for coronary artery disease and acute myocardial infarction: evidence for chronic over-expression of tumor necrosis factor alpha and vascular cells adhesion molecule-1. Int J Cardiol 2008; 130: 246-250.
• 119 Caliskan Y. et al. Hepatitis C virus infection in hemodialysis patients is not associated with insulin resistance, inflammation and atherosclerosis. Clin Nephrol 2009; 71: 147-157.
• 120 Sung J. et al. Hepatitis B virus seropositivity and the risk of stroke and myocardial infarction. Stroke 2007; 38: 1436-1441.
• 121 Haji SA. et al. Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation. J Heart Lung Transplant 2004; 23: 277-283.
• 122 Boddi M. et al. Hepatitis C virus RNA localization in human carotid plaques. J Clin Virol 2010; 47: 72-75.
• 123 Boddi M. et al. HCV infection facilitates asymptomatic carotid atherosclerosis: preliminary report of HCV RNA localization in human carotid plaques. Dig Liver Dis 2007; 39 Suppl (Suppl. 01) S55-60.
• 124 Tong DY. et al. Hepatitis B virus infection and coronary atherosclerosis: results from a population with relatively high prevalence of hepatitis B virus. World J Gastroenterol 2005; 11: 1292-1296.
• 125 Burnett MS. et al. Effects of hepatitis A vaccination on atherogenesis in a murine model. J Viral Hepat 2003; 10: 433-436.
• 126 Warren-Gash C. et al. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis 2009; 9: 601-610.
• 127 Madjid M. et al. Influenza and atherosclerosis: vaccination for cardiovascular disease prevention. Expert Opin Biol Ther 2005; 5: 91-96.
• 128 Naghavi M. et al. Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation 2000; 102: 3039-3045.
• 129 Phrommintikul A. et al. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J 2011; 32: 1730-1735.
• 130 Heffelfinger JD. et al. Influenza vaccination and risk of incident myocardial infarction. Hum Vaccin 2006; 2: 161-166.
• 131 Jackson LA. et al. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Am J Epidemiol 2002; 156: 634-640.
• 132 Auer J. et al. Influenza A and B IgG seropositivity and coronary atherosclerosis assessed by angiography. Heart Dis 2002; 4: 349-354.
• 133 Guan XR. et al. Influenza virus infection and risk of acute myocardial infarction. Inflammation 2008; 31: 266-272.
• 134 Naghavi M. et al. Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice. Circulation 2003; 10: 762-768.
• 135 Van Lenten BJ. et al. Influenza infection promotes macrophage traffic into arteries of mice that is prevented by D-4F, an apolipoprotein A-I mimetic peptide. Circulation 2002; 106: 1127-1132.
• 136 Haidari M. et al. Influenza virus directly infects, inflames, and resides in the arteries of atherosclerotic and normal mice. Atherosclerosis 2010; 208: 90-96.
• 137 Van Lenten BJ. et al. High-density lipoprotein loses its anti-inflammatory properties during acute influenza a infection. Circulation 2001; 103: 2283-2288.
• 138 Depairon M. et al. Premature atherosclerosis in HIV-infected individuals--focus on protease inhibitor therapy. AIDS 2001; 15: 329-334.
• 139 Grunfeld C. et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23: 1841-1849.
• 140 Hsue PY. et al. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation 2004; 109: 1603-1608.
• 141 Lo J. et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 2010; 24: 243-253.
• 142 Hulten E. et al. HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies. Heart 2009; 95: 1826-1835.
• 143 Currier JS. et al. Carotid artery intima-media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure. AIDS 2005; 19: 927-933.
• 144 Lebech AM. et al. Carotid intima-media thickness in HIV patients treated with antiretroviral therapy. Clin Physiol Funct Imaging 2007; 27: 173-179.
• 145 Kappert K. et al. Highly active antiretroviral therapy attenuates re-endothelialization and alters neointima formation in the rat carotid artery after balloon injury. J Acquir Immune Defic Syndr 2006; 43: 383-392.
• 146 Behrens GM. et al. Lipodystrophy syndrome in HIV infection: what is it, what causes it and how can it be managed?. Drug Saf 2000; 23: 57-76.
• 147 Asztalos BF. et al. Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients. Atherosclerosis 2006; 184: 72-77.
• 148 Badiou S. et al. Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?. Atherosclerosis 2003; 168: 107-113.
• 149 Stein JH. et al. Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation 2001; 104: 257-262.
• 150 Calza L. et al. Cardiovascular risk factors and ultrasound evaluation of carotid atherosclerosis in patients with HIV-1 infection. Int J STD AIDS 2009; 20: 683-689.
• 151 Coll B. et al. HIV-infected patients with lipodystrophy have higher rates of carotid atherosclerosis: the role of monocyte chemoattractant protein-1. Cytokine 2006; 34: 51-55.
• 152 Guaraldi G. et al. Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects. Atherosclerosis 2010; 208: 222-227.
• 153 Aoun S, Ramos E. Hypertension in the HIV-infected patient. Curr Hypertens Rep 2000; 2: 478-481.
• 154 Schillaci G. et al. Aortic stiffness in untreated adult patients with human immunodeficiency virus infection. Hypertension 2008; 52: 308-313.
• 155 Duffy P. et al. HIV Nef protein causes endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells. J Surg Res 2009; 156: 257-264.
• 156 Eugenin EA. et al. Human immunodeficiency virus (HIV) infects human arterial smooth muscle cells in vivo and in vitro: implications for the pathogenesis of HIV-mediated vascular disease. Am J Pathol 2008; 172: 1100-1111.
• 157 Mujawar Z. et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol 2006; 4: e365
• 158 Micheletti RG. et al. Coronary atherosclerotic lesions in human immunodeficiency virus-infected patients: a histopathologic study. Cardiovasc Pathol 2009; 18: 28-36.
• 159 Paton P. et al. Coronary artery lesions and human immunodeficiency virus infection. Res Virol 1993; 144: 225-231.
• 160 Tabib A. et al. Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients. Coron Artery Dis 2000; 11: 41-46.
• 161 Maggi P. et al. Atherosclerosis in HIV patients: a new face for an old disease?. AIDS Rev 2006; 8: 204-209.
• 162 Lobzin Iu V. et al. Effect of respiratory infections on the clinical course of coronary artery disease. Klin Med (Mosk). 2005; 83: 22-26.
• 163 Adam E. et al. High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. Lancet 1987; 2: 291-293.
• 164 Espinola-Klein C. et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection?. Stroke 2000; 31: 2127-2133.
• 165 Heltai K. et al. Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease. Atherosclerosis 2004; 173: 339-346.
• 166 Pesonen E. et al. Dual role of infections as risk factors for coronary heart disease. Atherosclerosis 2007; 192: 370-375.
• 167 Pesonen E. et al. Infections as a stimulus for coronary occlusion, obstruction, or acute coronary syndromes. Ther Adv Cardiovasc Dis 2009; 3: 447-454.
• 168 Shi Y, Tokunaga O. Chlamydia pneumoniae and multiple infections in the aorta contribute to atherosclerosis. Pathol Int 2002; 52: 755-763.
• 169 Raza-Ahmad A. et al. Evidence of type 2 herpes simplex infection in human coronary arteries at the time of coronary artery bypass surgery. Can J Cardiol 1995; 11: 1025-1029.
• 170 Susloparov MA. et al. The study of markers of herpes virus infections in myocardial ischemia. Mol Gen Mikrobiol Virusol 2005; 4: 36-40.
• 171 Sun Y. et al. Herpes simplex virus type 2 infection is a risk factor for hypertension. Hypertens Res 2004; 27: 541-544.
• 172 Alber DG. et al. Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse. Circulation 2000; 102: 779-785.
• 173 Alber DG. et al. Enhanced atherogenesis is not an obligatory response to systemic herpesvirus infection in the apoE-deficient mouse: comparison of murine gamma-herpesvirus-68 and herpes simplex virus-1. Arterioscler Thromb Vasc Biol 2002; 22: 793-798.
• 174 De Backer J. et al. Parameters of inflammation and infection in a community based case-control study of coronary heart disease. Atherosclerosis 2002; 160: 457-463.
• 175 Guan XR. et al. Respiratory syncytial virus infection and risk of acute myocardial infarction. Am J Med Sci 2010; 340: 356-359.
• 176 Liu SC. et al. Human parvovirus b19 infection in patients with coronary atherosclerosis. Arch Med Res 2009; 40: 612-617.
• 177 Grayston JT. Antibiotic treatment of atherosclerotic cardiovascular disease. Circulation 2003; 107: 1228-1230.
• 178 O'Connor CM. et al. Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. J Am Med Assoc 2003; 290: 1459-1466.
• 179 Grayston JT. et al. Azithromycin for the secondary prevention of coronary events. N Engl J Med 2005; 352: 1637-1645.
• 180 Cannon CP. et al. Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome. N Engl J Med 2005; 352: 1646-1654.
• 181 Jespersen CM. et al. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. Br Med J 2006; 332: 22-27.
• 182 Danesh J. Antibiotics in the prevention of heart attacks. Lancet 2005; 365: 365-367.
• 183 Epstein SE. et al. Insights into the role of infection in atherogenesis and in plaque rupture. Circulation 2009; 119: 3133-3141.
• 184 Grayston JT. Chlamydia pneumoniae and atherosclerosis. Clin Infect Dis 2005; 40: 1131-1132.
• 185 Beatty WL. et al. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 1994; 58: 686-699.
• 186 Kutlin A. et al. Effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on Chlamydia pneumoniae in a continuous-infection Model. Antimicrob Agents Chemother 2002; 46: 409-412.
• 187 Gieffers J. et al. Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment. Circulation 2001; 103: 351-356.