Abstract
The vascular endothelium acts as a selective barrier to regulate macromolecule exchange between the blood and tissues. However, the integrity of the endothelium barrier is compromised in an array of pathological settings, including ischemic disease and cancer, which are the leading causes of death worldwide. The resulting vascular hyperpermeability to plasma molecules as well as leukocytes then leads to tissue damaging edema formation and inflammation. The vascular endothelial growth factor A (VEGFA) is a potent permeability factor, and therefore a desirable target for impeding vascular hyperpermeability. However, VEGFA also promotes angiogenesis, the growth of new blood vessels, which is required for reperfusion of ischemic tissues. Moreover, edema increases interstitial pressure in poorly perfused tumors, thereby affecting the delivery of therapeutics, which could be counteracted by stimulating the growth of new functional blood vessels. Thus, targets must be identified to accurately modulate the barrier function of blood vessels without affecting angiogenesis, as well as to develop more effective pro- or anti-angiogenic therapies. Recent studies have shown that the VEGFA co-receptor neuropilin 1 (NRP1) could be playing a fundamental role in steering VEGFA-induced responses of vascular endothelial cells towards angiogenesis or vascular permeability. Moreover, NRP1 is involved in mediating permeability signals induced by ligands other than VEGFA. This review therefore focuses on current knowledge on the role of NRP1 in the regulation of vascular permeability signaling in the endothelium to provide an up-to-date landscape of the current knowledge in this field.
Highlights
The vascular system consists of a complex network of blood vessels organized as a closed circulatory system in all vertebrates as well as some invertebrates [1,2]
Recent studies have shown that the vascular endothelial growth factor A (VEGFA) co-receptor neuropilin 1 (NRP1) could be playing a fundamental role in steering VEGFA-induced responses of vascular endothelial cells towards angiogenesis or vascular permeability
While VEGFA is best known as an angiogenic growth factor, it was originally described as a vascular permeability factor because it disrupts endothelial barrier function and thereby increases vascular leakage and interstitial pressure [76]
Summary
The vascular system consists of a complex network of blood vessels organized as a closed circulatory system in all vertebrates as well as some invertebrates [1,2]. The vascular system carries blood through all the districts of the organism to deliver oxygen and nutrients, which are necessary for organ and tissue homeostasis, and to remove waste and catabolites. It does not surprise that the vascular system is the first organ system to form in the developing vertebrate embryos [3,4], at a time when blood vessels contribute to primitive hematopoietic development [5,6]. Circulating immune cells interact with blood vessels to extravasate and provide immunosurveillance and establish innate or adaptive immunity in pathological conditions [7]
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