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Likewise, the function of blood vessels depends on hormones that regulate blood pressure, blood coagulation, and inammation.To favor hormone delivery or blood transport into growing tissues, hormones promote angiogenesis, the proliferation of new blood vessels from preexisting vasculature.By acting systemically, hormones coordinate and integrate angiogenesis with other functions throughout the body.They also regulate blood vessel growth by controlling the production of local chemical mediators, often other hormones, but also growth factors, cytokines, enzymes, receptors, adhesion molecules, and metabolic factors, by vascular endothelial cells and other cells within the vicinity of capillaries.Proteolytic cleavage is a mechanism used frequently to generate proangiogenic and antiangiogenic protein mediators at specic sites.Proteolytic cleavage of extracellular matrix components releases smaller proangiogenic fragments from larger proteins, as well as sequestered proangiogenic growth factors and cytokines. Similarly, antiangiogenic peptides are generated via proteolysis of components of the ECM and the coagulation and brinolytic systems. Although proteolytically processed antiangiogenic fragments have long been known, little attention has been given to proteolytic cleavage as an important mechanism controlling hormone action on angiogenesis.Here, we review the regulation of angiogenesis by representative peptide hormones that are converted to proangiogenic or antiangiogenic molecules by proteolytic cleavage.The properties of these fragments versus those of their precursors, the regulation of the protease responsible for specic protein cleavage, and the selective expression of specic receptors and associated signaling pathways for each hormonal isoform are discussed within a wider context of health and disease, with the expectation that understanding the role of hormones in angiogenesis could open new therapeutic perspectives for Valganciclovir hydrochloride diseases resulting from angiogenic dysregulation.In the adult organism, the proliferation of blood vessels is key for the growth and function of female reproductive organs, such as the ovary and endometrium during the Apremilast menstrual cycle and the placenta and mammary gland during pregnancy. However, in most adult tissues, physiological angiogenesis is highly restricted, and capillary growth occurs only rarely and in association with repair processes such as wound and fracture healing.Disruption of the mechanisms controlling physiological angiogenesis has a major impact on health, as it underlies the pathogenesis of a growing list of diseases characterized by the overproliferation of blood vessels, including cancer, psoriasis, arthritis, retinopathies, obesity, asthma, and atherosclerosis.In addition, insufcient angiogenesis and abnormal vessel regression can lead to heart and brain ischemia, neurodegeneration, hypertension, osteoporosis, respiratory distress, preeclampsia, endometriosis, postpartum cardiomyopathy, and ovarian hyperstimulation syndrome. Hypoxia is an important stimulus for the physiological and pathological growth of blood vessels. It connects vascular oxygen supply to metabolic demand.Cells are normally oxygenated by diffused oxygen, but when tissues grow beyond the limit of oxygen diffusion, hypoxia triggers vessel growth by signaling through hypoxiainducible transcription factors that upregulate and downregulate the expression of proangiogenic and antiangiogenic factors, respectively. In the embryo, blood vessels originate from endothelial cell progenitors that migrate into avascular areas and form a primitive vessel network.This de novo formation of blood vessels, termed vasculogenesis, is followed by sprouting, branching, and stabilization in the process known as angiogenesis that utilizes existing vasculature to generate new vessels.Even though both vasculogenesis and angiogenesis have long been known to initiate a functional circulatory system during embryogenesis, that vasculogenesis also operates in the adult has been claried only recently.

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