Correlation of bacterial coinfection versus matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 expression in aortic aneurysm and atherosclerosis.

BACKGROUND: We searched for any relationship between Chlamydophila pneumoniae, Mycoplasma pneumoniae, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in aneurysmatic atherosclerotic lesions, and whether this relationship differed from that in atherosclerotic nonaneurysmatic lesions. METHODS: Twenty-eight tissue samples paired by age and sex were grouped as follows: group 1 included 14 nonaneurysmal atherosclerotic fragments obtained from abdominal aortas collected from necropsies; group 2 included 14 aneurysmatic atherosclerotic aortic fragments obtained from patients during corrective surgery. Immunohistochemistry reactions were evaluated for C pneumoniae, M pneumoniae, MMP-9, and TIMP-1 antigens. Both groups were compared using the Mann-Whitney test, and the correlations among variables were obtained using the Spearman correlation test. P ≤ 0.05 was considered statistically significant. RESULTS: C pneumoniae and M pneumoniae antigens were detected in 100% of cases. A higher amount of C pneumoniae (P = 0.005), M pneumoniae (P = 0.002), and MMP-9 (P = 0.021) was found in adventitia of group 2 with aneurysm. A positive correlation was found in the aneurysm group, as follows: intima C pneumoniae versus adventitia thickness (r = 0.70; P = 0.01), media C pneumoniae versus adventitia C pneumoniae (r = 0.75; P = 0.002), intima C pneumoniae versus media C pneumoniae (r = 0.8; P = 0.00), and adventitia C pneumoniae versus intima M pneumoniae (r = 0.54; P = 0.05); negative correlations were as follows: adventitia thickness and adventitia M pneumoniae (r = -0.65; P = 0.01), media MMP-9 and media thickness (r = -0.55; P = 0.04), TIMP-1 media versus adventitia C pneumoniae (r = -0.86; P = 0.00), and TIMP-1 media versus M pneumoniae intima (r = -0.67; P = 0.03). Nonaneurysmal atherosclerotic group 1 results are as follows: adventitia C pneumoniae versus TIMP-1 media (r = 0.75; P = 0.01) and media C pneumoniae and adventitia C pneumoniae (r = 0.59; P = 0.03). CONCLUSIONS: The present work favors a role for coinfection of both M pneumoniae and C pneumoniae in the development of aortic atherosclerotic aneurysm, with increased adventitial inflammation, inhibition of TIMP-1 activity, and increased collagen degradation.

Narrowed lumen of the right coronary artery in chronic Chagasic patients is associated with ischemic lesions of segmental thinnings of ventricles.

Thinning of myocardial segments, mainly at the apex and basal posterior region of left ventricle, are frequent lesions in chronic chagasic cardiopathy (CCC), but still without a well determined etiology. Previously we found severe myocardial microvascular dilatation that could cause ischemia in watershed regions. In this study we analyzed whether narrowness in epicardial coronary arteries in CCC might explain these thinned ventricular lesions. Two groups of dilated hearts with similar weights were compared: eleven hearts from patients with CCC versus four hearts from patients with dilated cardiomyopathy (IDCM). As normal controls we studied three non dilated normal weight hearts. There were no atherosclerotic plaques in the main branches of epicardial coronary arteries and cross-sectional luminal areas of proximal and distal segments were histologically measured. It was found that CCC hearts presented a lower mean luminal area in the right coronary artery (RCA) branch than IDCM, in proximal (4.3 +/- 1.4 vs 6.6 +/- 2.0 mm2; p=0.02) and in distal (1.6 +/- 1.0 vs 3.4 +/- 0.9 mm2; p=0.01) segments, with no statistical differences with normal hearts (2.7 +/- 1.3 and 1.5 +/- 0.3 mm2) in proximal (p=0.2) and distal (p=0.11) sections. In conclusion thinning of ventricular wall in CCC patients seems to be ischemic lesions in the peripheral territory irrigated by the right coronary artery, possibly due to a steal phenomenon by the left coronary, induced by micro vessels dilatation.

Density of Chlamydia pneumoniae is increased in fibrotic and calcified areas of degenerative aortic stenosis.

BACKGROUND: The process of aortic degeneration associated with calcified aortic stenosis shares many similarities with coronary artery atherosclerosis. Inflammation and infection are involved in both diseases. Chlamydia pneumoniae has been identified in atherosclerotic plaques. However, the studies about the presence of C. pneumoniae in degenerative aortic stenotic valves are not conclusive. OBJECTIVE: We investigated whether an association exists between the density of C. pneumoniae and fibrosis or calcification in aortic stenosis. DESIGN: Autopsy and surgical specimens were divided into 3 groups: Normal, 11 normal autopsy valves Atherosclerosis, 10 autopsy valves from patients with systemic atherosclerosis and no aortic stenosis and Aortic stenosis, 14 surgical specimens of aortic valves replaced due to aortic stenosis. SETTING: Heart Institute (InCor), University of São Paulo Medical School. PATIENTS: Aortic valves from patients aged 52+/-16 years, 69+/-9 years, and 71+/-8 years. INTERVENTION: Specimens were evaluated by immunohistochemical technique (to detect C. pneumoniae antigens), in situ hybridization, and electron microscopy (to quantify the density of C. pneumoniae in the valves). MEASUREMENTS: The aortic stenosis group was analyzed according to 3 subregions: aortic stenosis-preserved, peripheral preserved regions; aortic stenosis-fibrosis, peri-calcified fibrotic tissue; and aortic stenosis-calcification, calcified nodules. RESULTS: The median values of C. pneumoniae antigens were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, Aortic stenosis-preserved, Aortic stenosis-fibrosis, and Aortic stenosis-calcification, respectively. The amount of C. pneumoniae was greater in the Atherosclerosis and Aortic stenosis-calcification groups than in the Normal group (P<0.05). C. pneumoniae was greater in the Aortic stenosis group in the calcified and fibrotic regions than in preserved region (P<0.05). CONCLUSION: An association was found between the higher density of C. pneumoniae and fibrosis/calcification in stenotic aortic valves.

Polymerase chain reaction in endomyocardial biopsies for monitoring reactivation of Chagas' disease in heart transplantation: a case report and review of the literature.

Polymerase chain reaction (PCR) has been used to detect microbiological agent recurrence after heart transplantation of viral-induced cardiomyopathies. We report a case of reactivation of Chagas' disease after heart transplantation in which parasites could be detected in the endomyocardial biopsy using hematoxylin-eosin-stained sections, immunohistochemistry, and PCR for Trypanosoma cruzi DNA. Interestingly, PCR results remained positive in the endomyocardial biopsy 53 days after the beginning of successful treatment, pointing to the possibility of chronic persistence of parasites in the myocardium after the reactivation of Chagas' disease.

[Chlamydia pneumoniae and Mycoplasma pneumoniae in calcified nodes of stenosed aortic valves]. / Chlamydia pneumoniae e Mycoplasma pneumoniae nos nódulos de calcificação da estenose da valva aórtica.

OBJECTIVE: We investigated whether Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP) are present in aortic valve stenosis (AS). METHODS: Immunohistochemistry was utilized to identify CP antigens, in situ hybridization to identify MP DNA, and electron microscopy was used to evaluate the following three groups: Normal - 11 normal autopsy valves; Atherosclerosis - 10 autopsy valves from patients with systemic atherosclerosis and no AS; and AS - 14 surgical specimens of AS analyzed in 3 sub-regions: AS-Preserved - peripheral, preserved regions; AS-Fibrosis - peri-calcified fibrotic tissue; and AS-Calcification - calcified nodules. RESULTS: The positive area fraction of CP antigen median values were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, AS-Preserved, AS-Fibrosis, and AS-Calcification, respectively. CP density was significantly greater in Atherosclerosis and AS-Calcification than in Normal (P<0.05). Within the AS group, the amount of CP was greater in the Calcification and Fibrosis regions (P<0.05). MP-DNA positive area fraction (median values) were 0.12, 0.44, 0.07, 0.36, and 1.52 in groups Normal, Atherosclerosis, AS-Preserved, AS-Fibrosis, and AS-Calcification, respectively. The amount of MP-DNA was greater in AS-Calcification than in Normal (P<0.05). Within the AS group, MP-DNA was in larger quantity in the Calcification and Fibrosis regions (P<0.05). CONCLUSION: AS Calcified nodes present higher concentration of CP and MP suggesting that these bacteria may be associated with the development of calcification and inflammation. This adds novel similarities between AS and the atherosclerosis process, which may have infection mechanisms involved.

Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves.

Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage.

Coinfection with Mycoplasma pneumoniae and Chlamydia pneumoniae in ruptured plaques associated with acute myocardial infarction.

OBJECTIVE: To study atheromas, Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). METHODS: C. pneumoniae was studied with immunohistochemistry and M. pneumoniae with in situ hybridization (ISH), in segments of coronary arteries (SCA) as follows: group A - thrombosed ruptured plaques (TRP) of 23 patients who died due to acute myocardial infarction (AMI); group B - 23 nonruptured plaques (NRP) of group A patients; group C - NRP of 11 coronary patients who did not die due to AMI; and group D - 11 SCA from patients with dilated cardiomyopathy or Chagas' disease without atherosclerosis. RESULTS: The mean number of C. pneumoniae+ cells/400x in groups A, B, C, and D was, respectively, 3.3 +/- 3.6; 1.0 +/- 1.3; 1.2 +/- 2.4; and 0.4 +/- 0.3; and the percentage of M. pneumoniae area was, respectively, 3.9 +/- 3.5; 1.5 +/- 1.6; 0.9 +/- 0.9; and 0.4 +/- 0.2. More M. pneumoniae and C. pneumoniae were found in of group A than in group B (P<0.01). Good correlation was seen between the area of the vessel and the M. pneumoniae area in the plaque (r = 0.46; P=0.001) and between C. pneumoniae+ cells and CD4+ T lymphocytes (r = 0.42; P<0.01). The number of C. pneumoniae+ cells correlated with CD20+ B cells (r=0.48; P<0.01). CONCLUSION: M. pneumoniae and C. pneumoniae are more frequently found in TRP correlate with the intensity of the inflammation and diameter of the vessel (positive remodeling).

Chlamydia pneumoniae e Mycoplasma pneumoniae nos nódulos de calcificacão da estenose da valva aórtica / Chlamydia pneumoniae and Mycoplasma pneumoniae in calcified nodes of stenosed aortic valves

OBJETIVO: Investigar se chlamydia pneumoniae (CP) ou mycoplasma pneumoniae (MP) estão presentes na estenose da valva aórtica (EA). MÉTODOS: Imuno-histoquímica foi utilizada para identificar os antígenos de CP (Ag-CP), a hibridizacão in situ para identificar o DNA de MP, e microscopia eletrônica para avaliacão dos dois agentes, nos grupos: normal - 11 valvas normais de autópsia; aterosclerose - 10 valvas de pacientes com aterosclerose sistêmica de autópsia e sem EA; e EA - 14 espécimes cirúrgicos provenientes de pacientes com EA analisados em 3 sub-regiões: EA-preservada - regiões mais preservadas na periferia da valva; EA-fibrose - tecido fibrótico peri-calcificacão; e EA-calcificacão - nódulos calcificados. RESULTADOS: As medianas da fracão de área positiva para Ag-CP foram 0,09; 0,30; 0,18; 1,33; e 3,3 nos grupos acima descritos, respectivamente. A densidade de CP foi significativamente maior nos grupos aterosclerose e EA-calcificacão em relacão ao normal (p<0,05). Dentro do grupo EA, a quantidade de CP foi maior nas regiões de fibrose e calcificacão (p<0,05). As fracões de área positivas para MP-DNA (medianas) foram 0,12; 0,44; 0,07; 0,36; e 1,52 nos grupos acima descritos, respectivamente. A quantidade de MP-DNA foi maior na EA-calcificacão em relacão ao normal (p<0,05). Dentro do grupo EA, maior quantidade de MP-DNA foi encontrada nas regiões de calcificacão e fibrose (p<0,05). CONCLUSAO: Os nódulos de calcificacão da EA tinham maior concentracão de CP e MP sugerindo que essas bactérias possam estar associadas ao desenvolvimento de calcificacão e inflamacão, apontando novas semelhancas entre os processos de EA e aterosclerose, que podem ter mecanismos infecciosos envolvidos.

Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves

Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage

Co-infecção por Mycoplasma pneumoniae e Chlamydia pneumoniae em placas rotas associadas a infarto agudo do miocardiol / Coinfection with Mycoplasma Pneumoniae and Chlamydia Pneumoniae in ruptured plaques associated with acute myocardial infarction

OBJECTIVE: To study atheromas, Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). METHODS: C. pneumoniae was studied with immunohistochemistry and M. pneumoniae with in situ hybridization (ISH), in segments of coronary arteries (SCA) as follows: group A - thrombosed ruptured plaques (TRP) of 23 patients who died due to acute myocardial infarction (AMI); group B - 23 nonruptured plaques (NRP) of group A patients; group C - NRP of 11 coronary patients who did not die due to AMI; and group D - 11 SCA from patients with dilated cardiomyopathy or Chagas' disease without atherosclerosis. RESULTS: The mean number of C. pneumoniae+ cells/400x in groups A, B, C, and D was, respectively, 3.3±3.6; 1.0±1.3; 1.2±2.4; and 0.4±0.3; and the percentage of M. pneumoniae area was, respectively, 3.9±3.5; 1.5± 1.6; 0.9±0.9; and 0.4±0.2. More M. pneumoniae and C. pneumoniae were found in of group A than in group B (P<0.01). Good correlation was seen between the area of the vessel and the M. pneumoniae area in the plaque (r = 0.46; P=0.001) and between C. pneumoniae+ cells and CD4+ T lymphocytes (r = 0.42; P<0.01). The number of C. pneumoniae+ cells correlated with CD20+ B cells (r=0.48; P<0.01). CONCLUSION: M. pneumoniae and C. pneumoniae are more frequently found in TRP correlate with the intensity of the inflammation and diameter of the vessel (positive remodeling)