This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/2/348    most recent 01.ATV.0000152609.28569.e1v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Orlandi, A. Articles by Spagnoli, L. G. Search for Related Content PubMed PubMed Citation Articles by Orlandi, A. Articles by Spagnoli, L. G. Related Collections Animal models of human disease Apoptosis Smooth muscle proliferation and differentiation

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:348.)
© 2005 American Heart Association, Inc.

Vascular Biology

Modulation of Clusterin Isoforms Is Associated With All-Trans Retinoic Acid–Induced Proliferative Arrest and Apoptosis of Intimal Smooth Muscle Cells

Augusto Orlandi; Sabina Pucci; Alessandro Ciucci; Flavia Pichiorri; Amedeo Ferlosio; Luigi Giusto Spagnoli

From Anatomic Pathology, Tor Vergata University of Rome, Italy.

Correspondence to Augusto Orlandi, Anatomic Pathology Institute, Department of Biopathology and Image Diagnostics, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy. E-mail orlandi{at}uniroma2.it

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 -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.

Clusterin was detected in human arterial myointimal thickening and absent in the underlying media. Rat neointimal cells overexpressed clusterin and clusterin antisense oligonucleotide reduced proliferation and increased apoptosis. All-trans retinoic acid-induced proliferative arrest showed association with s-CLU reduction and n-CLU overexpression with apoptosis, supporting a different biological role of these isoforms.

Key Words: apolipoprotein J • smooth muscle cell heterogeneity • intimal thickening • -smooth muscle actin

This article has been cited by other articles:

				R. M. Moretti, M. M. Marelli, S. Mai, A. Cariboni, M. Scaltriti, S. Bettuzzi, and P. Limonta Clusterin Isoforms Differentially Affect Growth and Motility of Prostate Cells: Possible Implications in Prostate Tumorigenesis Cancer Res., November 1, 2007; 67(21): 10325 - 10333. [Abstract] [Full Text] [PDF]

				J. M. Albert, A. Gonzalez, P. P. Massion, H. Chen, S. J. Olson, Y. Shyr, R. Diaz, E. S. Lambright, A. Sandler, D. P. Carbone, et al. Cytoplasmic Clusterin Expression Is Associated with Longer Survival in Patients with Resected Non Small Cell Lung Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1845 - 1851. [Abstract] [Full Text] [PDF]

				A. Orlandi, A. Francesconi, M. Marcellini, A. Di Lascio, and L. G. Spagnoli Propionyl-L-carnitine Reduces Proliferation and Potentiates Bax-related Apoptosis of Aortic Intimal Smooth Muscle Cells by Modulating Nuclear Factor-{kappa}B Activity J. Biol. Chem., February 16, 2007; 282(7): 4932 - 4942. [Abstract] [Full Text] [PDF]