Role of Phosphoinositide 3-Kinases and Angiogenesis in Cardiovascular Diseases
Pp. 70-85 (16)
Cinzia Perrino, Giovanni Esposito, Giuseppe Gargiulo, Gianluigi Pironti, Gabriele G. Schiattarella and Massimo Chiariello
The regulation of angiogenesis, both its increase or decrease, could be
an important therapeutic target for a number of diseases. The role of angiogenesis
in atherosclerosis and other cardiovascular diseases is currently controversial.
Indeed, angiogenic therapy has been widely regarded as an attractive approach to
treat ischemic heart disease, but a variety of studies also suggest that
neovascularization contributes to the growth of atherosclerotic lesions and is a key
factor in plaque destabilization leading to rupture. Recent studies have shown that
the phosphatidylinositol 3-kinase (PI3K) family of enzymes plays an important
role in the regulation of tumor growth and angiogenesis. PI3Ks and their
downstream effector PKB/Akt can be activated by a variety of extracellular signals
and regulate a number of cellular processes including cell proliferation, survival,
protein synthesis, tumor growth and angiogenesis. Several lines of evidence
indicate that inhibition of PI3K suppresses angiogenesis and tumor growth.
Nonselective PI3K inhibitors, wortmannin and LY294002, are commonly used to
inhibit cancer cell proliferation and tumor growth, and sensitize tumor cells to the
treatment with chemotherapeutic drugs and radiation. This review will dissect the
role of the PI3Ks pathway in different animal models, and will describe possible
future directions for the development of novel therapeutic strategies to modulate
the angiogenetic process by regulating PI3K signaling.
Phosphatidylinositol 3-kinase (PI3Ks), angiogenesis, cardiovascular system.
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy.