Increased expression of MMP-9, PPAR a and Chlamydophila pneumoniae e Mycoplasma pneumoniae antigens in atherosclerostic aortic fragments with aneurysms

Introdução: Aneurisma de aorta é considerado uma doença inflamatória crônica, mas ainda é controverso se está relacionado a aterosclerose aos agentes infecciosos. Antígenos de Chlamydophila pneumoniae (CP) e Mycoplasma pneumoniae (MP) foram encontrados em grande quantidade nas placas instáveis que usualmente estão associadas a remodelamento positivo e inflamação do vaso. Metaloproteinase da matriz 9 (MMP-9) está implicada na fragilidade da parede vascular e na formação dos aneurismas. Os efeitos imunomodulatórios dos receptores ativados por proliferador de peroxissomo (PPARs) têm sido relacionados à aterosclerose. Objetivos: Comparar lesões ateroscleróticas graves com e sem aneurisma do ponto de vista inflamatório e infeccioso, analisando antígenos de MP e CP e expressão de MMP-9, TIMP-1 e PPARs. Métodos: No presente estudo quantificamos, através da técnica de imunoistoquímica, antígenos de MMP- 9, TIMP-1, PPARs a e , e dos agentes infecciosos CP e MP em fragmentos de aorta ateroscleróticos com aneurisma (n=14) e sem aneurisma (n=14). Resultados: A adventícia e o tecido adiposo periadventicial (TAP) dos aneurismas apresentaram intensa inflamação. Expressão de MMP-9 esteve aumentada no TAP e agentes infecciosos, TIMP-1 e PPAR a estiveram aumentados na adventícia e no TAP, sem diferença em relação a expressão de PPAR . Colágeno, TIMP-1 e PPARs estiveram positivamente correlacionados no grupo com aterosclerose, mas não no grupo com aneurisma. Conclusão: Nossos achados sugerem que aneurisma de aorta é uma complicação das lesões ateroscleróticas. Quantidade aumentada de Chlamydophila pneumoniae e Mycoplasma pneumoniae na adventícia e PAT sem correlação da resposta de TIMP-1 e PPARs são achados que estão associados com a presença de aneurisma nos segmentos de aorta ateroscleróticosIntroduction: Aortic aneurysm is considered a chronic inflammatory disease, but remains a controversial matter if it is related to atherosclerosis and infectious agents. Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) antigens were found in higher amount in unstable plaques that are usually associated to positive remodeling and vessel inflammation. Matrix metalloproteinase 9 (MMP-9) has been implicated in vascular wall fragility and aneurysm development. The immunemodulator effects of peroxisome proliferators - activated receptor (PPARs) have been related to atherosclerosis. Objectives: To compare severe atherosclerotic lesions with and without aneurysms by inflammatory and infectious point of view, analyzing MP and CP, MMP-9, TIMP-1 and PPARs antigens. Methods: In the present study we quantified, using immunohistochemistry technique, MMP-9, TIMP-1, PPAR a and and infectious agents CP and MP antigens in aortic atherosclerotic fragments with aneurysms. (n=14) and without aneurysms (n=14). Results: Adventitia and periadventitial adipose tissue (PAT) from aneurysms showed intense inflammation. MMP-9 expression has increased in PAT and the infectious agents, TIMP-1 and PPAR a were increased in adventitia and PAT in aneurysmatic group, without difference related to PPAR expression. Collagen, TIMP-1 and PPARs were positively correlated in atherosclerotic group, but it was not observed in aneurysmatic group. Conclusion: Our data have suggested that aortic aneurysm is a complication of aortic atherosclerotic lesions. Increased amount of Chlamydophila pneumoniae and Mycoplasma pneumoniae in the adventitia and PAT without a correlated TIMP-1 and PPARs response are findings that were associated with the presence of aneurysm in atherosclerotic aortic segment

Usefulness of qualitative polymerase chain reaction for Trypanosoma cruzi DNA in endomyocardial biopsy specimens of chagasic heart transplant patients

BACKGROUND: Chagas` disease reactivation (CDR) after heart transplantation is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. CDR affecting the myocardium induces lymphocytic myocarditis and should be distinguished from acute cellular rejection in endomyocardial biopsy (EMB) specimens. METHODS: We performed retrospectively qualitative polymerase chain reaction for T cruzi DNA using 2 sets of primers targeting nuclear DNA (nDNA) or kinetoplast DNA (kDNA) in 61 EMB specimens of 11 chagasic heart transplant recipients who presented with CDR. Thirty-five EMB specimens were obtained up to 6 months before (pre-CDR group) and 26 up to 2 years after the diagnosis of CDR. The control group consisted of 6 chagasic heart transplant recipients with 18 EMB specimens who never experienced CDR. RESULTS: Amplification of kDNA occurred in 8 of 35 (22.9%) EMB specimens of the pre-CDR group, in 5 of 18(27.8%) of the control group, and in 17 of 26(65.4%) EMB specimens obtained after the successful treatment of CDR. Amplification of nDNA occurred in 3 of 35 (8.6%) EMB specimens of the pre-CDR group, 0 of 18 (0%) of the control group, and 6 of 26 (23.1%) EMB specimens obtained after the successful treatment of CDR. CONCLUSIONS: Amplification of kDNA in EMB specimens is not specific for the diagnosis of CDR, occurring also in patients with no evidence of CDR (control group). However, amplification of nDNA occurred in a few EMB specimens obtained before CDR, but in none of the control group specimens. Qualitative PCR for T cruzi DNA in EMB specimens should not be used as a criterion for cure of CDR because it can persist positive despite favorable clinical evolution of the patients. J Heart Lung Transplant 2011;30:799-804 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP[09/50181-6

Gene Expression of Sirtuin-1 and Endogenous Secretory Receptor for Advanced Glycation End Products in Healthy and Slightly Overweight Subjects after Caloric Restriction and Resveratrol Administration

Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference (p = 0.011), TC (p = 0.007), HDL (p = 0.031), non-HDL (p = 0.025), ApoA1 (p = 0.011), and ApoB (p = 0.037) decreased in the CR group. However, TC (p = 0.030), non-HDL (p = 0.010), ApoB (p = 0.034), and HOMA-IR (p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 ± 0.71 ng/mL to 5.75 ± 2.98 ng/mL (p < 0.0001) and from 1.65 ± 1.81 ng/mL to 5.80 ± 2.23 ng/mL (p < 0.0001). esRAGE serum levels were similar in RSV (p = NS) and CR (p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV (r = 0.86; p < 0.0001) and in CR (r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction

Comparison of Resveratrol Supplementation and Energy Restriction Effects on Sympathetic Nervous System Activity and Vascular Reactivity: A Randomized Clinical Trial

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443; p = 0.002), triglycerides (r = 0.438; p = 0.002), apoA-I (r = 0.467; p = 0.001), apoB (r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021–1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction