The role of caveolin-1 mediating the effects of aldosterone-mediated Mineralocorticoid receptor activation / Siti Khairani Mohd Hafiz Ngoo

Mineralocorticoid receptor (MR) activation by aldosterone (ALDO) in the endothelial cells of the vascular system has been recognized as one of the many causes of hypertension. Previous studies from this laboratory has recently demonstrated that MR is present and functional in endothelial cells, co-localizes and co-immunoprecipitates with caveolin-1 (CAV-1), suggesting a role of CAV-1 in modulating MR function. This is further supported by the presence of caveolin binding motifs on MR as well as evidence showing that CAV-1 KO has reduced ALDO-mediated vascular damage as compared to WT mice, implicating an interaction between MR and Cav-1. Despite the mounting evidence that MR and CAV-1 are associated in endothelial cells, the cross talk between the pathways mediated by these proteins remains vague. This study was designed to elucidate (1) the genomic effects of ALDO on MR and CAV-1 proteins, (2) the non-genomic effects of ALDO on CAV-1 and ERKl/2 phosphorylation, as well as (3) the role of CAV-1 in modulating these effects.