Andrea Isidori

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Protezione cardiovascolare e renale nel diabete mellito: il ruolo dei PDE5 inibitori.

Cardiovascular and renal protection in diabetes mellitus: a role for PDE5 inhibitors.

Diabetes mellitus is associated a defective tissue repair, wound healing and pathological remodeling of the cardiovascular system. Tissue repair involves the interaction of vascular, immune and stem cells driven by coordinated signaling pathways that appears defective in diabetes. Which molecular mechanisms are impaired, however, remains unclear. Impaired repair capacity may derive from altered intracellular pathways, changes in cellular and/or extracellular response to stimuli or the complex interplay of all these factors.  In the cardiovascular system, cGMP signaling helps regulate many physiological processes such as vascular tone, platelet activity, cardiac contractility, renal fluid balance and cell growth. Reduced or dysfunctional cGMP production is involved in the pathogenesis of heart failure and hypertension. Inhibiting PDE5 (a cGMP-specific hydrolyzing enzyme) has been shown to have beneficial cardiovascular effects, through cardioprotection and modulation of inflammation. We have first demonstrated in human diabetes that PDE5 inhibitors exhibit anti-remodeling effects. Then,  using a bedside-to-bench approach with the advantage of novel screening strategy, we provided converging human and murine data on the signaling pathways involved in pharmacological modulation of tissue protection and repair in diabetes mellitus.