HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1451    most recent 01194.2006v2 01194.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Afilalo, J. Articles by Duque, G. Search for Related Content PubMed PubMed Citation Articles by Afilalo, J. Articles by Duque, G.

Age-related changes in lamin A/C expression in cardiomyocytes

¹Division of Internal Medicine, Department of Medicine, and ²Echocardiography Laboratory, Division of Cardiology, Department of Medicine, and ³Division of Geriatric Medicine, Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill University; ⁴Division of Experimental Medicine, Department of Medicine, McGill University; and ⁵Bank of Montreal Center for the Study of Heart Disease in Women and ⁶Bloomfield Center for Studies in Aging, Lady Davis Institute for Medical Research, Montréal, Québec, Canada

Submitted 31 October 2006 ; accepted in final form 16 May 2007

Lamin A and C (A/C) are type V intermediate filaments that form the nuclear lamina. Lamin A/C mutations lead to reduced expression of lamin A/C and diverse phenotypes such as familial cardiomyopathies and accelerated aging syndromes. Normal aging is associated with reduced expression of lamin A/C in osteoblasts and dermal fibroblasts but has never been assessed in cardiomyocytes. Our objective was to compare the expression of lamin A/C in cardiomyocytes of old (24 mo) versus young (4 mo) C57Bl/6J mice using a well-validated mouse model of aging. Lamin B1 was used as a control. Immunohistochemical and immunofluorescence analyses showed reduced expression of lamin A/C in cardiomyocyte nuclei of old mice (proportion of nuclei expressing lamin A/C, 9% vs. 62%, P < 0.001). Lamin A/C distribution was scattered peripherally and perinuclear in old mice, whereas it was homogeneous throughout the nuclei in young mice. Western blot analyses confirmed reduced expression of lamin A/C in nuclear extracts of old mice (ratio of lamin A/C to B1, 0.6 vs. 1.2, P < 0.01). Echocardiographic studies showed increased left ventricular wall thickness with preserved cavity size (concentric remodeling), increased left ventricular mass, and a slight reduction in fractional shortening in old mice. This is the first study to show that normal aging is associated with reduced expression and altered distribution of lamin A/C in nuclei of cardiomyocytes.

aging; laminopathy; nucleus; cardiomyopathy