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.
|Titolo:||ADAM-10 could mediate cleavage of N-cadherin promoting apoptosis in human atherosclerotic plaques: a morphological and immunohistochemical study|
|Data di pubblicazione:||2014|
|Citazione:||ADAM-10 could mediate cleavage of N-cadherin promoting apoptosis in human atherosclerotic plaques: a morphological and immunohistochemical study / Musumeci G; Coleman R; Imbesi R; Magro G; Parenti R; Szychlinska MA; Scuderi R; Cinà CS; Castorina S; Castrogiovanni P. - In: ACTA HISTOCHEMICA. - ISSN 0065-1281. - 116:7(2014), pp. 1148-1158.|
|Appare nelle tipologie:||1.1 Articolo in rivista|