Platelet-associated angiogenesis regulating factors: a pharmacological perspective

Platelets, in addition to maintaining hemostasis, also stimulate angiogenesis by generating and releasing, upon activation, factors that promote the growth of new blood vessels. To date, at least 20 angiogenesis-regulating factors have been identified in platelets, including both promoters and inhibitors. Platelet-derived angiogenesis regulators promote angiogenesis during wound healing, tumor growth, and in response to ischemia. Within platelets, angiogenesis regulators are primarily stored in alpha-granules, but are also found in the cytosol or derived from membrane lipids. Their release can be inhibited pharmacologically by anti-platelet agents, which consequently suppress platelet-stimulated angiogenesis. Several years ago, our research group discovered that platelets generate the angiogenesis inhibitor angiostatin independent of the activation state of platelets, and that platelet-derived angiostatin serves to limit the angiogenesis-stimulating effects of platelets. In this review, we summarize the current knowledge of platelet-associated angiogenesis regulators, how they impact angiogenesis, and how they are controlled pharmacologically.