Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes
Paneni, Francesco ; Costantino, Sarah ; Castello, Lorenzo ; Battista, Rodolfo ; Capretti, Giuliana ; Chiandotto, Sergio ; D'Amario, Domenico ; Scavone, Giuseppe ; Villano, Angelo ; Rustighi, Alessandra ; Crea, Filippo ; Pitocco, Dario ; Lanza, Gaetano ; Volpe, Massimo ; Del Sal, Giannino ; Lüscher, Thomas F. ; Cosentino, Francesco
In: European Heart Journal, 2015, vol. 36, no. 13, p. 817-828
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- The present study demonstrates that Pin1 is a common activator of key pathways involved in diabetic vascular disease in different experimental settings including primary human endothelial cells, knockout mice, and diabetic patients. Gene silencing and genetic disruption of Pin1 prevent hyperglycaemia-induced mitochondrial oxidative stress, endothelial dysfunction, and vascular inflammation. Moreover, we have translated our findings to diabetic patients. In line with our experimental observations, Pin1 up-regulation is associated with impaired flow-mediated dilation, increased oxidative stress, and plasma levels of adhesion molecules. In perspective, these findings may provide the rationale for mechanism-based therapeutic strategies in patients with diabetes