The Hemostatic System as a Regulator of Angiogenesis

Abstract

Angiogenesis is the process of sprouting and configuring new blood vessels from pre-existing blood vessels, whereas the hemostatic system maintains the liquid flow of blood by regulating platelet adherence and fibrin deposition. Both systems normally appear quiescent, yet both systems remain poised for repair of injury. With vessel injury, a rapid sequence of reactions must occur to occlude the vessel wall defect and prevent hemorrhage. Activated platelets link the margins of the defect and form a provisional barrier that is quickly enmeshed with polymerized fibrin. This clot structure initially requires immobilized vascular endothelial cells to anchor the clot and prevent further bleeding. Thereafter, endothelial cells at the clot margins become mobile, dismantling and invading the cross-linked fibrin structure to rebuild a new vessel wall.Although the positive and negative regulators that control the delicate balance of platelet reactivity and fibrin deposition have been elucidated over the past four decades, analogous proteins that control endothelial cell growth and inhibition have only been discovered within the past decade. Hemostasis and angiogenesis are becoming increasingly inter-related. Proteins generated by the hemostatic system coordinate the spatial localization and temporal sequence of clot/endothelial cell stabilization followed by endothelial cell growth and repair of a damaged blood vessel. We focus here on the regulation of angiogenesis during vessel repair mediated by proteins secreted by platelets and derived as cryptic fragments from the coagulation cascade and fibrinolytic system.

Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

“…However, it has recently been shown that isolated platelets from cancer patients contain more VEGF than isolated platelets from healthy controls (Salven et al, 1999b) and a very recent study have demonstrated that the serum VEGF concentrations in cancer patients with normal platelet counts were higher than in healthy controls with normal platelet counts (Lee et al, 2000). Platelet aggregation may contribute to tumour progression by release of a variety of vasoactive and proangiogenic substances in the tumour (Browder et al, 2000) and to metastasis by facilitating adherence of disseminated tumour cells to capillary walls at distant sites (Hejna et al, 1999). Therefore, although the preoperative serum VEGF concentration is affected by in vitro degranulation of platelets, the increased platelet-derived VEGF may influence the biology of a present tumour in vivo, and may presumably reflect tumour burden at the time of surgery.…”

Activated Platelets Provide a Functional Microenvironment for the Antiangiogenic Fragment of Histidine-Rich Glycoprotein

“…Both processes are normally quiescent but are consistent host responses to vessel injury or tumor growth. Interestingly, several inhibitors of angiogenesis are found within the hemostatic pathway (7,8), one of them being HRG. The reason for this dual function is thought to be the requirement for strict regulation of the angiogenic process during wound healing.…”

“…Examples of positive regulators of angiogenesis found in platelets are VEGF-A, VEGF-C, platelet-derived growth factor, and fibroblast growth factor-2, whereas negative regulators include thrombospondin, platelet factor 4 (PF4), and plasminogen activator inhibitor type-1 (7,8). Platelets are anuclear cellular fragments, derived from megakaryocytes in the bone marrow, and play a crucial role in regulating blood hemostasis.…”

Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide

“…The majority of these are cranial, consisting of clustered, fine cortical porosity and are argued to be the result of bleeding of vasculature associated with the muscles of mastication, such as the temporalis and pterygoids (Ortner et al, 1999, 2001; Ortner & Ericksen, 1997). Capillary proliferation is part of the inflammatory response to the presence of extravascular blood; these new vessels act as a delivery system for phagocytic cells of the innate immune system to aid in the removal of hemorrhagic material (Browder, Folkman, & Pirie‐Shepherd, 2000). Ortner & others argue that this hypervascular (angiogenic) response to extravasated blood will result in fine (<1 mm across) abnormal porosity at sites of subperiosteal hemorrhage as new capillaries create pathways through the bony cortex (Klaus, 2017; Ortner et al, 2001; Figure 1).…”