Title:New therapeutic effects of cilostazol in patients with ischemic disorders
Volume: 13
Issue: 3
Author(s): Federico Biscetti, Gianfranco Ferraccioli and Andrea Flex
Affiliation:
Keywords:
Cilostazol, peripheral arterial disease, angiogenesis, vascular endothelial growth factor.
Abstract: Cilostazol (CIL) is effective for the treatment of patients with peripheral arterial disease
(PAD). CIL is an orally administered drug with multiple effects, including anti-platelets aggregation,
favorable functions on plasmatic lipids and vasodilator ones, but how these effects might be related to
improvement in patients walking affected by PAD is not fully understood. The latest data demonstrate
that nitric oxide (NO) is induced by CIL through endothelial nitric oxide synthase (eNOS) activation via a cyclic-AMP
(cAMP)/ protein kinase A (PKA)- and PI3K/Akt- dependent mechanism. This mechanism is also responsible for the
vasodilatation dependent on endothelium which characterized patients receiving CIL. Other investigators have found that
CIL notably reduces the exercise-induced host-inflammatory response in PAD patients, and consequently it improves lipid
hydroperoxides and cell-adhesion molecule levels. We recently reported that CIL is able to cause neoangiogenesis in vivo
by stimulating the production of proangiogenic proteins, such as vascular endothelial growth factor (VEGF), that increase
levels of Endothelial progenitor cells (EPCs) and the formation of new blood vessels.
The mechanisms of action of this drug are several and are not clear and established. The objective of the present review is
to analyze the existing data about the therapeutic effects of CIL, with the purpose of providing practical indications about
this topic for the management of subjects affected by ischemic disorders.
