Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat.
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.
Ratajczak
Philippe
P
Inserm-U572/IFR 6, Hopital Lariboisière, 41 Boulevard de la Chapelle, 75475 Paris Cedex 10, France.
Damy
Thibaud
T
Heymes
Christophe
C
Oliviéro
Patricia
P
Marotte
Françoise
F
Robidel
Estelle
E
Sercombe
Richard
R
Boczkowski
Jorge
J
Rappaport
Lydie
L
Samuel
Jane-Lise
JL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1; D051244:Caveolin 3; D022461:Caveolins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006321:Heart / Q000254:growth & development; D006333:Heart Failure / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism
C495537:Cav1 protein, rat; C495549:Cav3 protein, rat; D051242:Caveolin 1; D051244:Caveolin 3; D022461:Caveolins; D019001:Nitric Oxide Synthase