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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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    Title
    • Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes
    Author
    • Paneni, Francesco. Cardiology and Cardiovascular Research, Institute of Physiology and University Hospital, Zürich, Switzerland
    • Costantino, Sarah. Cardiology and Cardiovascular Research, Institute of Physiology and University Hospital, Zürich, Switzerland
    • Castello, Lorenzo. Cardiology, Department of Clinical and Molecular Medicine, University of Rome ‘Sapienza', Rome, Italy
    • Battista, Rodolfo. Internal Medicine Unit, Civil Hospital, Sora, Italy
    • Capretti, Giuliana. Cardiology, Department of Clinical and Molecular Medicine, University of Rome ‘Sapienza', Rome, Italy
    • Chiandotto, Sergio. Cardiology, Department of Clinical and Molecular Medicine, University of Rome ‘Sapienza', Rome, Italy
    • D'Amario, Domenico. Department of Cardiovascular Medicine, Catholic University, Rome, Italy
    • Scavone, Giuseppe. Diabetes Care Unit, Internal Medicine, Catholic University, Rome, Italy
    • Villano, Angelo. Department of Cardiovascular Medicine, Catholic University, Rome, Italy
    • Rustighi, Alessandra. Laboratorio Nazionale CIB, AREA Science Park and Department of Life Sciences, University of Trieste, Trieste, Italy
    • Crea, Filippo. Department of Cardiovascular Medicine, Catholic University, Rome, Italy
    • Pitocco, Dario. Diabetes Care Unit, Internal Medicine, Catholic University, Rome, Italy
    • Lanza, Gaetano. Department of Cardiovascular Medicine, Catholic University, Rome, Italy
    • Volpe, Massimo. IRCCS Neuromed, Pozzilli, Italy
    • Del Sal, Giannino. Laboratorio Nazionale CIB, AREA Science Park and Department of Life Sciences, University of Trieste, Trieste, Italy
    • Lüscher, Thomas F.. Cardiology and Cardiovascular Research, Institute of Physiology and University Hospital, Zürich, Switzerland
    • Cosentino, Francesco. Cardiology and Cardiovascular Research, Institute of Physiology and University Hospital, Zürich, Switzerland
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:298655
    Summary
    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