Objective: Implantation of a left ventricular assist device (LVAD) in the failing human heart initiates structural and functional changes termed reverse remodeling. Mechanical unloading improves cardiac adrenergic responsiveness and lipid metabolism, processes regulated by caveolar function. We tested the hypothesis that mechanical unloading alters the expression of caveolins and these changes are linked to altered expression of markers of reverse remodeling. Methods: Paired human myocardial samples were obtained from patients who received an LVAD as a bridge to cardiac transplantation. Transcript levels were measured using real-time Q-RT-PCR in RNA prepared from 34 pairs of formalin-fixed myocardial tissue blocks. Caveolin-1 and -3 protein levels were determined from frozen tissue ( n = 5) by Western blots. Caveolin-3 localization was demonstrated by immunohistochemistry. Results: Caveolin-1 protein levels were upregulated in all LVAD-patients after mechanical unloading ( P = 0.002). Caveolin-1 mRNA was increased in 76% of the patients ( n = 34, P
