A study on immunopathogenetic mechanisms of atherosclerotic process caused by chronic infection of Chlamydia pneumoniae in rats (Ratus novergicus).
OBJECTIVE
this study was aimed to determine the correlations between duration of Chlamydia pneumoniae infection and the development of atherosclerotic process in white-rats' (Ratus novergicus) aorta.


METHODS
this is an experimental study which examined the expression of TNFa, IL-1b, IL-8, adhesion molecule of VCAM-1 and the development of foam cells associated with atherosclerotic process in white-rats' aorta. There were 32 male rats, +/- 6 weeks of age, divided into 4 groups: control group (K) without infection, and 3 groups with infection through nasal and oral inoculation of Chlamydia pneumoniae by single dose of 5 x 105 in amount of 35 microl. The first group (P1) was preserved for 5(1/2) months period, the second group (P2) was preserved for 7(1/2) months and the third group (P3) was preserved for 9(1/2) months. At the end of study, histological slides were made from aortic tissues in order to study the development of atherosclerotic process by examining foam cells and cytokines expression of TNFa, IL-1b, IL-8 and VCAM-1. Foam cells examination was performed by Hematoxcillin-eosin staining, while indirect immunohistochemistry staining was used to examine the expression of TNFa, IL-1b, IL-8 and VCAM-1. Afterward, the amount of foam cells and cytokines expression was measured. The study result was analyzed by ANOVA.


RESULTS
there was increased expression of TNFa, IL-1b, IL-8, VCAM-1and increased foam cells formation (extended atherosclerosis area) in the aortic tissues infected by Chlamydia pneumoniae (5(1/2) months, 7(1/2) months and 9(1/2) months), which was significantly different compared to the control group. The result of ANOVA revealed that the most important factor in tissue injury is foam cells development induced by VCAM-1 and IL-8 in all of phases (characterized by most abundant neutrophil infiltration). It indicated the infection caused by extracellular pathogenic agent, which established the fatty streak (acute phase) in 5(1/2) months period. In the group with 7(1/2) months infection period, TNFa also had important roles (characterized by increased monocytes and lymphocytes infiltration), indicating that there was negative-gram pathogenic agent with intracellular infection, which caused a progressive atherosclerotic process, and development of fibrosis / atherosclerotic plaque (sub acute phase). In 9(1/2) months infection period, there was large thrombus containing a lot of leukocytes in the aorta (chronic phase).


CONCLUSIONS
based on the result of this study, it may be concluded that Chlamydia pneumoniae may cause atherosclerotic process in aorta. Extracellular infection of Chlamydia pneumoniae occurs in all of phases and intracellular infection begins in sub-acute phase. On 5(1/2) months period, fatty streak is developed (acute phase); on 7(1/2) months period, there is atherosclerotic plaque (sub acute phase); and on 9(1/2) period, there is large thrombus containing a lot of leukocytes (a progressive chronic phase).
Aziz
Azirya
A
Department of Anatomy, Faculty of Medicine, Andalas University, Padang, Indonesia.
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D023521:Chlamydophila Infections / Q000150:complications* / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1