Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat.

Abstract

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 alpha 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 alpha 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.

• Authors: Philippe Ratajczak, Thibaud Damy, Christophe Heymes, Patricia Oliviéro, Françoise Marotte, Estelle Robidel, Richard Sercombe, Jorge Boczkowski, Lydie Rappaport, Jane-Lise Samuel
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 57 Issue 2 Pg. 358-69 (Feb 2003) ISSN: 0008-6363 [Print] England
• PMID: 12566108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cav1 protein, rat
• Cav3 protein, rat
• Caveolin 1
• Caveolin 3
• Caveolins
• Nitric Oxide Synthase

Topics

• Aging (metabolism)
• Animals
• Caveolae (metabolism)
• Caveolin 1
• Caveolin 3
• Caveolins (metabolism)
• Cytosol (metabolism)
• Heart (growth & development)
• Heart Failure (metabolism)
• Microscopy, Fluorescence
• Myocardial Infarction (metabolism)
• Myocardium (metabolism)
• Nitric Oxide Synthase (metabolism)
• Rats
• Rats, Wistar
• Sarcolemma (metabolism)