Department of Microbiology, Immunology and Cancer Biology, The University of Virginia, Charlottesville, VA, 22908, USA.
Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Angiogenesis. 2023 Aug;26(3):313-347. doi: 10.1007/s10456-023-09876-7. Epub 2023 Apr 15.
In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but are often done so without the normal feedback mechanisms that regulate the ordinary spatial and temporal patterns of blood vessel formation. Thus, pathological angiogenesis presents new challenges yet new opportunities for the design of vascular-directed therapies. Here, we provide an overview of recent insights into blood vessel development and highlight novel therapeutic strategies that promote or inhibit the process of angiogenesis to stabilize, reverse, or even halt disease progression. In our review, we will also explore several additional aspects (the angiogenic switch, hypoxia, angiocrine signals, endothelial plasticity, vessel normalization, and endothelial cell anergy) that operate in parallel to canonical angiogenesis mechanisms and speculate how these processes may also be targeted with anti-angiogenic or vascular-directed therapies.
在多细胞生物中，血管生成是指从预先存在的血管中形成新血管的过程，是生长和发育所必需的。血管生成、发芽、内套叠、融合血管生成以及血管选择、血管拟态和淋巴管生成等不同机制是新血管形成的基础。在许多病理条件下，如癌症、动脉粥样硬化、关节炎、银屑病、子宫内膜异位症、肥胖症和 SARS-CoV-2（COVID-19），发育性血管生成过程被重现，但通常没有正常的反馈机制来调节血管形成的正常时空模式。因此，病理性血管生成为血管靶向治疗的设计带来了新的挑战和新的机遇。在这里，我们概述了最近对血管发育的深入了解，并强调了促进或抑制血管生成过程以稳定、逆转甚至停止疾病进展的新治疗策略。在我们的综述中，我们还将探讨几个平行于经典血管生成机制的附加方面（血管生成开关、缺氧、血管分泌信号、内皮细胞可塑性、血管正常化和内皮细胞失能），并推测这些过程也可以通过抗血管生成或血管靶向治疗来靶向。
