PPARγ in coronary atherosclerosis: in vivo expression pattern and correlations with hyperlipidemic status and statin treatment.

OBJECTIVE: Peroxisome proliferator-activated receptor-γ (PPARγ) is involved in regulation of macrophage inflammation and in atherosclerosis. Herein we investigate the influence of statin treatment on PPARγ expression in coronary artery disease. METHOD: PPARγ expression was investigated in coronary atherosclerotic atherectomies (N=48) and arteries (N=12) from patients with stable or unstable coronary syndromes or undergoing cardiac transplantation for end-stage ischemic cardiomyopathy, respectively, by immunohistochemistry. Plaque components and tissue factor immunoreactivity were also investigated. Atherectomies were obtained from de novo culprit lesions of hypercholesterolemic (16 statin-treated and 16 untreated) and normolipidemic (N=16) patients. Furthermore, PPARγ expression was evaluated in patients peripheral blood monocytes and in monocytic U937 cells after atorvastatin incubation, by Western blot analysis. RESULT: PPARγ expression was higher in coronary plaques and peripheral blood monocytes of statin-treated patients, and it significantly increased in monocytes after 24h atorvastatin incubation (p<0.05). Intra-plaque macrophage content, atheroma, neoangiogenesis and hemorrhage, and circulating CRP levels were lower in statin-treated than untreated hypercholesterolemic patients and comparable with normolipidemic subjects. PPARγ immunoreactivity was localized to neointima and media, its distribution pattern being different from that of tissue factor. CONCLUSION: PPARγ expression was enhanced in statin-treated patients with different distribution and behavior as compared to atheroma, macrophage content, tissue factor immunoreactivity and serum CRP. In vitro studies showed increased PPARγ expression in monocytes after atorvastatin incubation. These findings provide further evidence as to the protective role of statins in coronary artery disease and their influence on PPARγ expression in coronary plaques and on the inflammatory status of patients.

Verrucoid lesions of mitral valve in a dog with features of inflammatory myofibroblastic tumor.

We report a mitral valve lesion detected at autopsy in a 9-year-old male German Shepherd dog suffering from mild mitral regurgitation. Gross examination of the heart showed exophitic, noncontiguous lesions involving the atrial aspect of both mitral leaflets. Microscopic evaluation of the mitral lesions disclosed a diffuse proliferation of myofibroblasts with little atypia, arranged loosely and rather randomly, within a myxoid stroma and associated with inflammatory cells identified as CD138+ plasma cells, CD68+ macrophages, and eosinophils. The myofibroblastic proliferation we describe is quite similar to previously described inflammatory myofibroblastic tumor (IMT), a very rare lesion, exceptionally found in the human heart.

Asymptomatic inflammatory myofibroblastic tumor of the heart: immunohistochemical profile, differential diagnosis, and review of the literature.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an uncommon lesion, mainly occurring in children and young adults and extremely rare in the heart. IMTs are composed of differentiated myofibroblastic cells accompanied by inflammatory cells. Cardiac IMTs are considered biologically benign, but they may have fatal consequences depending upon the peculiarity of site. Because of their rarity in the heart, most knowledge is based on extracardiac lesions that have uncertain behaviour. METHODS AND RESULTS: We investigated the morphologic features and the immunohistochemical profile of an intracardiac IMT, arising in the right outflow tract of an asymptomatic 11-month-old boy, by using a large panel of antibodies, many of them previously reported in extracardiac IMTs only. Results were compared with data of literature. After complete surgical excision of the tumor, the patient is disease-free at 1 year of follow-up. CONCLUSIONS: The present case showed morphologic and immunohistochemical features characteristic of IMT. Immunohistochemistry was helpful for characterization and differential diagnosis. The immunoreactivity pattern (including calponin expression) was similar to that of extracardiac IMTs except for anaplastic lymphoma kinase 1 immunoreactivity, lacking in this benign intracardiac IMT but usually associated to favourable prognosis in extracardiac IMTs.

Angiogenesis, tumor necrosis factor-alpha and procoagulant factors in coronary artery giant aneurysm of a fatal infantile Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an infantile febrile illness of unknown origin characterized by clinical, laboratory and histopathologic features of systemic vasculitis. METHODS AND RESULTS: We report a 3-month-old female infant with incomplete KD who suddenly died despite intravenous immunoglobulin, aspirin, steroid and heparin treatment. Postmortem examination confirmed the echocardiographically detected giant coronary aneurysms and showed occlusive thrombosis in the giant aneurysm of the left anterior descending coronary artery, associated with neoangiogenesis, macrophage infiltration and immunostaining for tissue factor (a strong initiator of the coagulation cascade), thrombopoietin receptor and tumour necrosis factor-alpha. CONCLUSIONS: These findings show the association of angiogenesis, tumor necrosis factor-alpha and procoagulant factors, with macrophage infiltration in coronary artery aneurysms of a fatal infantile KD.