Objectives - Clusterin is a heterodimeric glycoprotein which is implicated in several biological processes. The nuclear (n-CLU) and cytoplasmic secreted (s-CLU) isoforms have recently been described, but their role is still unclear. The aim of this study is to investigate the expression of clusterin and its isoforms during proliferative arrest and apoptosis of vascular smooth muscle cells (SMCs). Methods and Results - Clusterin expression was evaluated by immunohistochemistry and Western blotting in human arteries and rat aortas. In human diffuse myointimal thickening, clusterin was detected in cell cytoplasm and extracellular space, whereas it was practically absent in the media. In rat aortas 15 days after ballooning, intimal cells (IT cells) overexpressed s-CLU and n-CLU, the latter mainly in the inner neointima; clusterin expression decreased at 60 days. In vitro, IT cells maintained high clusterin expression and its antisense markedly reduced proliferation and increased apoptosis. Western blotting showed that all-trans retinoic acid-induced proliferative arrest and increased α-smooth muscle actin expression did associate to s-CLU and B-myb reduction, whereas bax-related apoptosis was associated to a shift from the s-CLU to n-CLU isoform. Conclusions - Clusterin overexpression characterized neointimal SMCs; s-CLU expression decreased in IT cells during all-trans retinoic acid-induced proliferative arrest and redifferentiation, whereas n-CLU overexpression was characteristic of apoptosis.

Orlandi, A., Pucci, S., Ciucci, A., Pichiorri, F., Ferlosio, A., Spagnoli, L.g. (2005). Modulation of clusterin isoforms is associated with all-trans retinoic acid-induced proliferative arrest and apoptosis of intimal smooth muscle cells. ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, 25(2), 348-353 [10.1161/01.ATV.0000152609.28569.e1].

Modulation of clusterin isoforms is associated with all-trans retinoic acid-induced proliferative arrest and apoptosis of intimal smooth muscle cells

ORLANDI, AUGUSTO;PUCCI, SABINA;CIUCCI, ALESSANDRA;FERLOSIO, AMEDEO;SPAGNOLI, LUIGI GIUSTO
2005-02-01

Abstract

Objectives - Clusterin is a heterodimeric glycoprotein which is implicated in several biological processes. The nuclear (n-CLU) and cytoplasmic secreted (s-CLU) isoforms have recently been described, but their role is still unclear. The aim of this study is to investigate the expression of clusterin and its isoforms during proliferative arrest and apoptosis of vascular smooth muscle cells (SMCs). Methods and Results - Clusterin expression was evaluated by immunohistochemistry and Western blotting in human arteries and rat aortas. In human diffuse myointimal thickening, clusterin was detected in cell cytoplasm and extracellular space, whereas it was practically absent in the media. In rat aortas 15 days after ballooning, intimal cells (IT cells) overexpressed s-CLU and n-CLU, the latter mainly in the inner neointima; clusterin expression decreased at 60 days. In vitro, IT cells maintained high clusterin expression and its antisense markedly reduced proliferation and increased apoptosis. Western blotting showed that all-trans retinoic acid-induced proliferative arrest and increased α-smooth muscle actin expression did associate to s-CLU and B-myb reduction, whereas bax-related apoptosis was associated to a shift from the s-CLU to n-CLU isoform. Conclusions - Clusterin overexpression characterized neointimal SMCs; s-CLU expression decreased in IT cells during all-trans retinoic acid-induced proliferative arrest and redifferentiation, whereas n-CLU overexpression was characteristic of apoptosis.
feb-2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/08 - ANATOMIA PATOLOGICA
English
Myocytes, Smooth Muscle; Animals; Apoptosis; Humans; Clusterin; TRPM Cation Channels; Rats; Proto-Oncogene Proteins c-bcl-2; Transcription Factors; Gene Expression Regulation; Molecular Chaperones; Oligodeoxyribonucleotides, Antisense; Glycoproteins; Trans-Activators; Cell Division; Uterus; Cell Cycle Proteins; Aorta, Thoracic; Mesenteric Arteries; bcl-2-Associated X Protein; DNA-Binding Proteins; Aorta; Balloon Dilation; Ion Channels; Cell Nucleus; Tunica Intima; Membrane Proteins; Protein Isoforms; Cells, Cultured; Muscle, Smooth, Vascular; Rats, Wistar; Tretinoin; Female
Orlandi, A., Pucci, S., Ciucci, A., Pichiorri, F., Ferlosio, A., Spagnoli, L.g. (2005). Modulation of clusterin isoforms is associated with all-trans retinoic acid-induced proliferative arrest and apoptosis of intimal smooth muscle cells. ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, 25(2), 348-353 [10.1161/01.ATV.0000152609.28569.e1].
Orlandi, A; Pucci, S; Ciucci, A; Pichiorri, F; Ferlosio, A; Spagnoli, Lg
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/38984
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