© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat
aInserm-U572/IFR 6, Hopital Lariboisière, 41 Boulevard de la Chapelle, 75475 Paris Cedex 10, France
bCNRS-UPR 646/IFR 6, Faculté de médecine Lariboisière, Saint-Louis, IFR 6, France
cInserm U408, Hôpital Bichat Université D Diderot, Paris, France
* Corresponding author. Tel.: +33-144-631-735; fax: +331-48-742-315 janelyse.samuel{at}inserm.lrb.ap-hop-paris.fr
Objective: Caveolins, the structural proteins of caveolae, modulate numerous signaling pathways including Nitric Oxide (NO) production. Among the caveolin family, caveolin-1 and -3 are mainly expressed in endothelial and muscle cells, respectively. In this study, we investigate whether (i) changes in caveolin abundance and/or distribution occur during cardiac aging and failure in rat, and (ii) the process could influence NO synthase (NOS) activity. Methods: Using immunohistolabelling and Western blot approaches, expression and distribution of caveolins were analysed in adult (Ad), senescent (S-Sh) and myocardial infarction-induced failing (S-MI) hearts. NOS3/caveolin-1 interactions were evaluated by immunoprecipitation assays. Results: At the microscope level, caveolin-1 distribution in the endothelial cells was unchanged between the groups. Conversely the typical distribution of caveolin-3 in myocyte sarcolemma was dramatically altered in S-MI rats, resulting in a heterogeneous pattern throughout the septum. Total abundance of caveolin-1 and -3 remained stable whatever the group. In the fractions free of caveolae (Triton X-100 soluble), the levels of caveolin-1
and -3 increased with aging (+20%, and +104%, P<0.05 versus Ad, respectively) and were further enhanced in S-MI (+25%, +30%, P<0.05, P<0.001 versus S-Sh respectively). In these fractions, NOS3/caveolin-1 complexes increased as well. In addition, NOS activity was negatively correlated to caveolin-1 level in the cytosolic fractions. Conclusions: We demonstrate that dissociation of caveolin from caveolae is associated with aging and heart failure, the process being related to the decreased NOS activity.
KEYWORDS Aging; Capillaries; Heart failure; Sarcolemma
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