*A Hidden Organism, Chlamydia in the Age of Atherosclerosis DOI: http://dx.doi.org/10.5772/intechopen.109745*

risk factors of cardiovascular and cerebrovascular diseases: potential therapeutical options. Open Neuroimaging Journal. 2008;**2**(1):20-24

[64] Rizzo M, Corrado E, Coppola G, Muratori I, Novo G, Novo S. Markers of inflammation are strong predictors of subclinical and clinical atherosclerosis in women with hypertension. Coronary Artery Disease. 2009;**20**(1):15-20

[65] Halvorsen B, Otterdal K, Dahl TB, Skjelland M, Gullestad L, Øie E, et al. Atherosclerotic plaque stability—what determines the fate of a plaque? Progress in Cardiovascular Diseases. 2008;**51**(3):183-194

[66] Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: a multifactorial process. Experimental and Clinical Cardiology. 2002;**7**(1):40-53

[67] Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proceedings of the National Academy of Sciences of the United States of America. 1995;**92**(18):8264-8268

[68] Cahill PA, Redmond EM. Vascular endothelium – gatekeeper of vessel health. Atherosclerosis. 2016;**248**:97-109

[69] von Eckardstein A, Rohrer L. Transendothelial lipoprotein transport and regulation of endothelial permeability and integrity by lipoproteins. Current Opinion in Lipidology. 2009;**20**(3):197-205

[70] O'Keefe JH, Gheewala NM, O'Keefe JO. Dietary strategies for ımproving post-prandial glucose, lipids, ınflammation, and cardiovascular health. Journal of the American College of Cardiology. 2008;**51**(3):249-255

[71] Montecucco F, Mach F. Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis. Rheumatology. 2008;**48**(1):11-22

[72] Zhang C. The role of inflammatory cytokines in endothelial dysfunction. Basic Research in Cardiology. 2008;**103**(5):398-406

[73] Athyros VG, Kakafika AI, Karagiannis A, Mikhailidis DP. Do we need to consider inflammatory markers when we treat atherosclerotic disease? Atherosclerosis. 2008;**200**(1):1-12

[74] Lin FY, Lin YW, Huang CY, Chang YJ, Tsao NW, Chang NC, et al. GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, ınduces lectinlike oxidized low-density lipoprotein receptor 1 expression in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits. Journal of Immunology. 2011;**186**(7):4405-4414

[75] Oörni K, Pentikäinen MO, Ala-Korpela M, Kovanen PT. Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions. Journal of Lipid Research. 2000;**41**(11):1703-1714

[76] Inia JA, O'Brien ER. Role of heat shock protein 27 in modulating atherosclerotic ınflammation. Journal of Cardiovascular Translational Research. 2021;**14**(1):3-12

[77] Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nature Immunology. 2004;**5**(10):975-979

[78] Lee GL, Yeh CC, Wu JY, Lin HC, Wang YF, Kuo YY, et al. TLR2 promotes vascular smooth muscle cell chondrogenic differentiation and

consequent calcification via the concerted actions of osteoprotegerin suppression and IL-6–mediated RANKL induction. Arteriosclerosis, Thrombosis, and Vascular Biology. 2019;**39**(3):432-445

[79] Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W, et al. A Definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. Circulation. 1995;**92**(5):1355-1374

[80] Hansson GK, Libby P, Schönbeck U, Yan ZQ. Innate and adaptive ımmunity in the pathogenesis of atherosclerosis. Circulation Research. 2002;**91**(4):281-291

[81] Bodi V, Sanchis J, Nunez J, Mainar L, Minana G, Benet I, et al. Uncontrolled immune response in acute myocardial infarction. American Heart Journal. 2008;**156**(6):1065-1073

[82] Gordon S. Pattern recognition receptors. Cell. 2002;**111**(7):927-930

[83] Matsuura E, Kobayashi K, Lopez LR. Atherosclerosis in autoimmune diseases. Current Rheumatology Reports. 2009;**11**(1):61-69

[84] Shor A, Kuo CC, Patton DL. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. South African Medical Journal. 1992;**82**(3):158-161

[85] Saikku P, Mattila K, Nieminen MS, Huttunen JK, Leinonen M, Ekman MR, et al. Serological evidence of an association of a novel chlamydia, twar, with chronic coronary heart disease and acute myocardial infarction. The Lancet. 1988;**332**(8618):983-986

[86] Campbell LA, Kuo C, cho. Chlamydia pneumoniae — an infectious risk factor for atherosclerosis? Nature Reviews. Microbiology. 2004;**2**(1):23-32

[87] Watson C, Alp NJ. Role of Chlamydia pneumoniae in atherosclerosis. Clinical Science. 2008;**114**(8):509-531

[88] Izadi M, Fazel M, Akrami M, Saadat SH, Pishgoo B, Nasseri MH, et al. Chlamydia pneumoniae in the atherosclerotic plaques of coronary artery disease patients. Acta Medica Iranica. 2013;**51**(12):864-870

[89] Kuo CC, Coulson AS, Campbell LA, Cappuccio AL, Lawrence RD, Wang SP, et al. Detection of Chlamydia pneumoniae in atherosclerotic plaques in the walls of arteries of lower extremities from patients undergoing bypass operation for arterial obstruction. Journal of Vascular Surgery. 1997;**26**(1):29-31

[90] Vikatmaa P, Lajunen T, Ikonen TS, Pussinen PJ, Lepäntalo M, Leinonen M, et al. Chlamydial lipopolysaccharide (cLPS) is present in atherosclerotic and aneurysmal arterial wall—cLPS levels depend on disease manifestation. Cardiovascular Pathology. 2010;**19**(1):48-54

[91] Otani T, Nishihira K, Azuma Y, Yamashita A, Shibata Y, Asada Y, et al. Chlamydia pneumoniae is prevalent in symptomatic coronary atherosclerotic plaque samples obtained from directional coronary atherectomy, but its quantity is not associated with plaque ınstability: an ımmunohistochemical and molecular study. Clinical. Pathology. 2022;**15**:2632010X2211251

[92] Assar O, Nejatizadeh A, Dehghan F, Kargar M, Zolghadri N. Association of Chlamydia pneumoniae ınfection with atherosclerotic plaque formation. Global Journal of Health Science. 2015;**8**(4):260

[93] Farrell C, bloth B, Nielsen H, Daugharty H, Lundman T, Svehag Se. A survey for circulating ımmune complexes in patients with acute myocardial

*A Hidden Organism, Chlamydia in the Age of Atherosclerosis DOI: http://dx.doi.org/10.5772/intechopen.109745*

ınfarction. Scandinavian Journal of Immunology. 2008;**6**(12):1233-1240

[94] Mfl L-V, Kj H, Agarwal R, Nl B, Virella G, Investigators V. Pro-apoptotic and ınflammatory markers enhance the ability of MDA-LDL in circulating ımmune complex to predict acute myocardial ınfarction in the VADT Study. Diabetes. 2018:67(Supplement\_1):430-P

[95] Glader C. The proatherogenic properties of lipoprotein(a) may be enhanced through the formation of circulating immune complexes containing Chlamydia pneumoniaespecific IgG antibodies. European Heart Journal. 2000;**21**(8):639-646

[96] Tertov VV, Orekhov AN, Sayadyan KS, Serebrennikov SG, Kacharava AG, Lyakishev AA, et al. Correlation between cholesterol content in circulating immune complexes and atherogenic properties of CHD patients' serum manifested in cell culture. Atherosclerosis. 1990;**81**(3):183-189

[97] Dahlén GH. Indications of an autoimmune component in LP(a) associated disorders. European Journal of Immunogenetics. 1994;**21**(5):301-312

[98] Dahlén GH, Boman J, Birgander LS, Lindblom B. Lp(a) lipoprotein, IgG, IgA and IgM antibodies to Chlamydia pneumoniae and HLA class II genotype in early coronary artery disease. Atherosclerosis. 1995;**114**(2):165-174

[99] Li H, Förstermann U. Nitric oxide in the pathogenesis of vascular disease. The Journal of Pathology. 2000;**190**(3):244-254

[100] Kern J, Maass V, Rupp J, Maass M. Proliferative stimulation of the vascular endothelin-1 axis in vitro and ex vivo by infection with Chlamydia pneumoniae. Thrombosis and Haemostasis. 2009;**102**(10):743-753

[101] Wang B, Zhang L, Zhang T, Wang H, Zhang J, Wei J, et al. Chlamydia pneumoniae ınfection promotes vascular smooth muscle cell migration through a toll-like receptor 2-related signaling pathway. Infection and Immunity. 2013;**81**(12):4583-4591

[102] Deniset JF, Cheung PKM, Dibrov E, Lee K, Steigerwald S, Pierce GN. Chlamydophila pneumoniae ınfection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host ımmune response. The American Journal of Pathology. 2010;**176**(2):1028-1037

[103] Flego D, Bianco M, Quattrini A, Mancini F, Carollo M, Schiavoni I, et al. Chlamydia pneumoniae modulates human monocyte-derived dendritic cells functions driving the induction of a Type 1/Type 17 inflammatory response. Microbes and Infection. 2013;**15**(2):105-114

[104] Liu W, He P, Cheng B, Mei CL, Wang YF, Wan JJ. Chlamydia pneumoniae disturbs cholesterol homeostasis in human THP-1 macrophages via JNK-PPARγ dependent signal transduction pathways. Microbes and Infection. 2010;**12**(14-15):1226-1235

[105] Zhao GJ, Mo ZC, Tang SL, Ouyang XP, He PP, Lv YC, et al. Chlamydia pneumoniae negatively regulates ABCA1 expression via TLR2-Nuclear factor-kappa B and miR-33 pathways in THP-1 macrophagederived foam cells. Atherosclerosis. 2014;**235**(2):519-525

[106] Tumurkhuu G, Dagvadorj J, Porritt RA, Crother TR, Shimada K, Tarling EJ, et al. Chlamydia pneumoniae hijacks a host autoregulatory IL-1β loop to drive foam cell formation and accelerate atherosclerosis. Cell Metabolism. 2018;**28**(3):432-448.e4

[107] Laitinen K, Laurila A, Pyhälä L, Leinonen M, Saikku P. Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits. Infection and Immunity. 1997;**65**(11):4832-4835

[108] Moazed TC, Kuo C, Patton DL, Grayston JT, Campbell LA. Experimental rabbit models of Chlamydia pneumoniae infection. The American Journal of Pathology. 1996;**148**(2):667-676

[109] Blessing E, Lin TM, Campbell LA, Rosenfeld ME, Lloyd D, Kuo CC. Chlamydia pneumoniae ınduces ınflammatory changes in the heart and aorta of normocholesterolemic C57BL/6J mice. Infection and Immunity. 2000;**68**(8):4765-4768

[110] Blessing E, Campbell LA, Rosenfeld ME, Kuo CC. Chlamydia pneumoniae and hyperlipidemia are co-risk factors for atherosclerosis: ınfection prior to ınduction of hyperlipidemia does not accelerate development of atherosclerotic lesions in C57BL/6J mice. Infection and Immunity. 2002;**70**(9):5332-5334

[111] Lantos I, Endrész V, Virok DP, Szabó A, Lu X, Mosolygó T, et al. Chlamydia pneumoniae ınfection exacerbates atherosclerosis in ApoB100 only/LDLR −/− mouse strain. BioMed Research International. 2018;**2018**:1-12

[112] Sorrentino R, Yilmaz A, Schubert K, Crother TR, Pinto A, Shimada K, et al. A single infection with Chlamydia pneumoniae is sufficient to exacerbate atherosclerosis in ApoE deficient mice. Cellular Immunology. 2015;**294**(1):25-32

[113] Fong IW, Chiu B, Viira E, Fong MW, Jang D, Mahony J. Rabbit model for Chlamydia pneumoniae infection. Journal of Clinical Microbiology. 1997;**35**(1):48-52

**202** [114] Zafiratos MT, Cottrell JT, Manam S, Henderson KK, Ramsey KH, Murthy AK. Tumor necrosis factor receptor superfamily members 1a and 1b contribute to exacerbation of atherosclerosis by Chlamydia pneumoniae in mice. Microbes and Infection. 2019;**21**(2):104-108

[115] Chen S, Shimada K, Zhang W, Huang G, Crother TR, Arditi M. IL-17A ıs proatherogenic in high-fat dietınduced and chlamydia pneumoniae ınfection-accelerated atherosclerosis in mice. Journal of Immunology. 2010;**185**(9):5619-5627

[116] Muhlestein JB, Anderson JL, Hammond EH, Zhao L, Trehan S, Schwobe EP, et al. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation. 1998;**97**(7):633-636

[117] Anderson JL, Muhlestein JB. The ACADEMIC study in perspective (azithromycin in coronary artery disease: elimination of myocardial ınfection with Chlamydia). The Journal of Infectious Diseases. 2000;**181**(s3):S569-S571

[118] O'Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, et al. Azithromycin for the secondary prevention of coronary heart disease events. Journal of the American Medical Association. 2003;**290**(11):1459

[119] Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, et al. Azithromycin for the secondary prevention of coronary events. The New England Journal of Medicine. 2005;**352**(16):1637-1645

[120] Cannon CP, Braunwald E, McCabe CH, Grayston JT, Muhlestein B, Giugliano RP, et al. Antibiotic treatment of chlamydia pneumoniae after acute coronary syndrome. The New England Journal of Medicine. 2005;**352**(16):1646-1654

*A Hidden Organism, Chlamydia in the Age of Atherosclerosis DOI: http://dx.doi.org/10.5772/intechopen.109745*

[121] Fong IW, Chiu B, Viira E, Jang D, Fong MW, Peeling R, et al. Can an antibiotic (macrolide) prevent chlamydia pneumoniae -ınduced atherosclerosis in a rabbit model? Clinical and Diagnostic Laboratory Immunology. 1999;**6**(6):891-894

[122] Rothstein NM, Quinn TC, Madico G, Gaydos CA, Lowenstein CJ. Effect of azithromycin on murine arteriosclerosis exacerbated by Chlamydia pneumoniae. The Journal of Infectious Diseases. 2001;**183**(2):232-237

[123] Phillips S, Quigley BL, Timms P. Seventy years of chlamydia vaccine research – limitations of the past and directions for the future. Frontiers in Microbiology. 2019;**10**:70

[124] Birkelund S, Christiansen G. Chlamydia trachomatis and chlamydia pneumoniae vaccines. In: Ellis & Brodeur, editor, New Bacterial Vaccines. Landes bioscience/Kluwer Academic/ Plenum Publishers. 2003. p. 91-109

[125] Li W, Gudipaty P, Li C, Henderson KK, Ramsey KH, Murthy AK. Intranasal immunization with recombinant chlamydial protease-like activity factor attenuates atherosclerotic pathology following Chlamydia pneumoniae infection in mice. Immunology and Cell Biology. 2019;**97**(1):85-91

[126] Lu X, Xia M, Endresz V, Faludi I, Szabo A, Gonczol E, et al. Impact of multiple antigenic epitopes from ApoB100, hHSP60 and Chlamydophila pneumoniae on atherosclerotic lesion development in Apobtm2SgyLdlrtm1Her J mice. Atherosclerosis. 2012;**225**(1):56-68

[127] Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial ınfarction in patients with average cholesterol levels.

The New England Journal of Medicine. 1996;**335**(14):1001-1009

[128] Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999;**100**(3):230-235

[129] Khush KK, Waters D. Lessons from the PROVE-IT trial. Higher dose of potent statin better for high-risk patients. Cleveland Clinic Journal of Medicine. 2004;**71**(8):609-616

[130] Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. The New England Journal of Medicine. 2008;**359**(21):2195-2207

[131] Albert MA, Danielson E, Rifai N, Ridker PM, for the PRINCE Investigators. Effect of Statin Therapy on C-Reactive Protein Levels. Journal of the American Medical Association. 2001;**286**(1):64

[132] Poznyak AV, Bharadwaj D, Prasad G, Grechko AV, Sazonova MA, Orekhov AN. Anti-ınflammatory therapy for atherosclerosis: focusing on cytokines. International Journal of Molecular Sciences. 2021;**22**(13):7061

[133] Nardulli M, Durlach V, Pepe G, Anglés-Cano E. Mechanism for the homocysteine-enhanced antifibrinolytic potential of lipoprotein(a) in human plasma. Thrombosis and Haemostasis. 2005;**94**(07):75-81

[134] Almer G, Frascione D, Pali-Schöll I, Vonach C, Lukschal A, Stremnitzer C, et al. Interleukin-10: an anti-ınflammatory marker to target atherosclerotic lesions via PEGylated liposomes. Molecular Pharmaceutics. 2013;**10**(1):175-186
