المؤلفون: Marino Labinaz, Henry F. Mizgala, Virginia M. Walley, Michael R. Garvin, Edward R. O'Brien, Klaus Pels

المصدر: Cardiovascular Research. 35:241-249

مصطلحات موضوعية: Adult, Male, Pathology, medicine.medical_specialty, Time Factors, Adolescent, Physiology, Gene Expression, Graft vs Host Disease, Coronary Disease, chemistry.chemical_compound, Physiology (medical), Plasminogen Activator Inhibitor 1, medicine, Humans, RNA, Messenger, In Situ Hybridization, Urokinase, business.industry, Vascular disease, Cell migration, medicine.disease, Coronary Vessels, Immunohistochemistry, Urokinase-Type Plasminogen Activator, Coronary arteries, Transplantation, medicine.anatomical_structure, chemistry, Plasminogen activator inhibitor-1, Heart Transplantation, Cardiology and Cardiovascular Medicine, business, Plasminogen activator, medicine.drug, Artery

الوصف: Objectives: Recent studies suggest that alterations in tissue thrombolysis as well as the inward migration of cells may be specific events that contribute to coronary artery narrowing after cardiac transplantation. Plasminogen activators and inhibitors play a central role in governing not only tissue thrombolysis, but also vascular cell migration. The purpose of this study was to examine arterial wall expression of the plasminogen activation system in coronary arteries during graft vascular disease initiation and progression. Methods: Using in situ hybridization and immunocytochemistry, the expression patterns of uPA and PAI-1 in coronary arteries from cardiac allografts were compared to those of young individuals without disease. Results: Both PAI-1 and uPA were over-expressed early after transplantation and as late as 27 months post grafting. Over-expression of these molecules preceded morphological evidence of graft vascular disease. Of special note was the adventitial expression of uPA and PAI-1 in microvessels and myofibroblasts. In contrast, the expression of uPA and PAI-1 in normal coronary arteries was confined to endothelial cells of the central lumen, as well as low levels of expression in intimal and medial smooth muscle cells. Conclusions: Despite morphologic similarities between normal and transplant coronary arteries, differences were noted in the vascular expression pattern of uPA and PAI-1. The exact role of these molecules in graft vascular disease requires further study; however, it is intriguing to consider that a local imbalance in the plasminogen system may contribute to arterial wall thrombosis and/or excessive cell migration and the genesis of complex vascular lesions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4be8179f68427c0b7ef0875610f317e3Test
https://doi.org/10.1016/s0008-6363Test(97)00088-6

المؤلفون: John H. Connelly, Ivan P. Uray, Peter J.A. Davies, O. Howard Frazier, Heinrich Taegtmeyer

المصدر: Cardiovascular research. 59(1)

مصطلحات موضوعية: Adult, CD36 Antigens, medicine.medical_specialty, Physiology, Caveolin 3, Caveolin 2, Blotting, Western, Caveolin 1, Myocardial Ischemia, Adrenergic, Klinikai orvostudományok, Caveolins, Physiology (medical), Internal medicine, Caveolin, Gene expression, medicine, Cluster Analysis, Humans, RNA, Messenger, Heart Failure, business.industry, Reverse Transcriptase Polymerase Chain Reaction, Myocardium, Lipid metabolism, Orvostudományok, Middle Aged, Immunohistochemistry, Transplantation, Endocrinology, Heart-Assist Devices, Cardiology and Cardiovascular Medicine, business, Atrial Natriuretic Factor

الوصف: Objective: Implantation of a left ventricular assist device (LVAD) in the failing human heart initiates structural and functional changes termed reverse remodeling. Mechanical unloading improves cardiac adrenergic responsiveness and lipid metabolism, processes regulated by caveolar function. We tested the hypothesis that mechanical unloading alters the expression of caveolins and these changes are linked to altered expression of markers of reverse remodeling. Methods: Paired human myocardial samples were obtained from patients who received an LVAD as a bridge to cardiac transplantation. Transcript levels were measured using real-time Q-RT-PCR in RNA prepared from 34 pairs of formalin-fixed myocardial tissue blocks. Caveolin-1 and -3 protein levels were determined from frozen tissue ( n = 5) by Western blots. Caveolin-3 localization was demonstrated by immunohistochemistry. Results: Caveolin-1 protein levels were upregulated in all LVAD-patients after mechanical unloading ( P = 0.002). Caveolin-1 mRNA was increased in 76% of the patients ( n = 34, P

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd1511666f4671f7e5c31400d5174699Test
https://pubmed.ncbi.nlm.nih.gov/12829176Test

المؤلفون: S E, Hughes

المصدر: Cardiovascular research. 32(3)

مصطلحات موضوعية: Adult, Male, Arteriosclerosis, Gene Expression, Receptor Protein-Tyrosine Kinases, Arteries, Filaggrin Proteins, Middle Aged, Protein-Tyrosine Kinases, Immunohistochemistry, Receptors, Fibroblast Growth Factor, Muscle, Smooth, Vascular, Fibroblast Growth Factors, Humans, Receptor, Fibroblast Growth Factor, Type 3, Female, Receptor, Fibroblast Growth Factor, Type 4, RNA, Messenger, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 2, In Situ Hybridization, Aged

الوصف: Aberrant expression of FGF-1 and FGF-2 may be central to the atherosclerotic disease process, promoting both intimal hyperplasia and plaque neovascularisation. FGF-1 and FGF-2 mediate their biological effects by binding to a family of specific high-affinity cell surface receptors with protein tyrosine kinase activity. Four receptors have been identified in the human (FGFR1/flg gene product, FGFR2/bek gene product, FGFR3 and FGFR4), but little is known of their in vivo tissue distribution. Characterisation of the spatial distribution of the FGFR multigene family in both normal and atherosclerotic arteries is a prerequisite to further define the functional role of FGF-1 and FGF-2 in atherosclerosis. The objective of this study was to examine the cell-type-specific expression of the FGFR multigene family members in both normal and atherosclerotic human arteries.FGFR expression was investigated immunocytochemically with polyclonal antisera to FGFR1-4 and by in situ hybridisation using FGFR1-4 riboprobes in archival material. Total cellular mRNA was analysed using poly d(T) and the levels correlated with the expression of FGFR1-4 mRNA.At the protein level, FGFR1-4 were expressed in the medial smooth muscle cells and adventitial vessels of normal arteries. In simple and advanced lesions, the expression profiles of FGFR1-4 showed variability between individual arteries, and cell-type-specific differential FGFR expression was apparent. Widespread co-expression of FGFR1 and FGFR2 was observed in intimal smooth muscle cells, foam cells and the plaque microvasculature of simple and advanced lesions. FGFR3 and FGFR4 exhibited more restricted patterns of distribution within the plaque. In situ hybridisation with poly d(T) confirmed high cellular transcriptional activity in archival atherosclerotic lesions. The high levels of total cellular mRNA and FGFR protein were not always reciprocated at the FGFR1-4 mRNA level, and only FGFR1 and FGFR2 mRNA transcripts were abundant in intimal lesions.These data provide evidence to suggest involvement of the FGF-FGFR multigene families in human atherogenesis. Differential FGFR expression in plaque subtypes may reflect distinct differences in receptor function which may be relevant to lesion progression during atherosclerosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::e66c10ffbab5f3abbc1caa9017b51a6eTest
https://pubmed.ncbi.nlm.nih.gov/8881516Test