title: ADAM-10 could mediate cleavage of N-cadherin promoting apoptosis in human atherosclerotic lesions leading to vulnerable plaque: a morphological and immunohistochemical study.
abstract: Atherosclerosis remains a major cause of mortality. Whereas the histopathological progression of atherosclerotic lesions is well documented, much less is known about the development of unstable or vulnerable plaque, which can rupture leading to thrombus, luminal occlusion and infarct. Apoptosis in the fibrous cap, which is rich in vascular smooth muscle cells (VSMCs) and macrophages, and its subsequent weakening or erosion seems to be an important regulator of plaque stability. The aim of our study was to improve our knowledge on the biological mechanisms that cause plaque instability in order to develop new therapies to maintain atherosclerotic plaque stability and avoid its rupture. In our study, we collected surgical specimens from atherosclerotic plaques in the right or left internal carotid artery of 62 patients with evident clinical symptoms. Histopathology and histochemistry were performed on wax-embedded sections. Immunohistochemical localization of caspase-3, N-cadherin and ADAM-10 was undertaken in order to highlight links between apoptosis, as expressed by caspase-3 immunostaining, and possible roles of N-cadherin, a cell-cell junction protein in VSMCs and macrophages that provides a pro-survival signal reducing apoptosis, and ADAM-10, a "disintegrin and metalloproteases" that is able to cleave N-cadherin in glioblastomas. Our results showed that when apoptosis, expressed by caspase-3 immunostaining, increased in the fibrous cap, rich in VSMCs and macrophages, the expression of N-cadherin decreased. The decreased N-cadherin expression, in turn, was linked to increased ADAM-10 expression. This study shows that apoptotic events are probably involved in the vulnerability of atherosclerotic plaque.
authors.affiliation: Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy. Electronic address: g.musumeci@unict.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.affiliation: Department of Anatomy & Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Raymond
authors.initials: R
authors.lastname: Coleman
authors.affiliation: Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Imbesi
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.affiliation: Department of Bio-Medical Sciences, Section of Physiology, University of Catania, Catania, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Parenti
authors.affiliation: Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Marta Anna
authors.initials: MA
authors.lastname: Szychlinska
authors.affiliation: Department of Medical and Pediatric Sciences, University of Catania, Catania, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Scuderi
authors.affiliation: Fondazione Mediterranea "G.B. Morgagni, 95125, Catania, Italy.
authors.forename: Claudio Salvatore
authors.initials: CS
authors.lastname: Cinà
authors.affiliation: Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy; Fondazione Mediterranea "G.B. Morgagni, 95125, Catania, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Castorina
authors.affiliation: Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Castrogiovanni
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072197:ADAM10 Protein; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D050197:Atherosclerosis / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000201:enzymology* / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; C505407:CASP3 protein, human; D053148:Caspase 3; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: ADAM-10; Atherosclerotic plaque; Caspase-3; N-cadherin; Vascular smooth muscle cells.