Reconciling VEGF With VPF: The Importance of Increased Vascular Permeability for Stroma Formation in Tumors, Healing Wounds, and Chronic Inflammation.
Reconciling VEGF With VPF: The Importance of Increased Vascular Permeability for Stroma Formation in Tumors, Healing Wounds, and Chronic Inflammation.
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VPF抑制VEGF：血管通透性增加对肿瘤、伤口愈合和慢性炎症基质形成的重要性。
DOI：
10.3389/fcell.2021.660609
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发表时间：
2021
影响因子：
5.5
通讯作者：
Dvorak HF
中科院分区：
文献类型：
--
作者：
Dvorak HF
人们普遍认为血管内皮生长因子(VEGF)通过对血管内皮细胞的直接促有丝分裂和促运动作用来诱导血管生成。然而，只有当内皮细胞在非常低的血清浓度(0.1%)下培养时才能检测到这些活性，而在体内血管生成部位的血清水平高得多的情况下，这些活性是不可能发生的。这一难题可以通过回顾血管内皮生长因子的原始功能来解决，即一种极其有效的血管渗透因子(VPF)。在体内，VPF/VEGF增加了微血管的通透性，使整个血浆渗入组织中，在那里它经历了表达在肿瘤和宿主结缔组织细胞上的组织因子的凝结，从而沉积纤维蛋白并产生血清。通过提供组织支持和局部重新编程细胞的基因表达模式，纤维蛋白和血清可以共同解释血管结缔组织基质的形成。总之，通过增加血管通透性，VPF/VEGF触发了“伤口愈合反应”，启动了一个基本的病理生理过程，诱导成熟的间质，这不仅存在于愈合的伤口中，也存在于实体肿瘤和慢性炎症性疾病中。一旦由血管通透性增加启动，这种反应可能很难被阻止，可能导致抗血管内皮生长因子疗法在治疗癌症方面的有限成功。
It is widely believed that vascular endothelial growth factor (VEGF) induces angiogenesis by its direct mitogenic and motogenic actions on vascular endothelial cells. However, these activities are only detected when endothelial cells are cultured at very low (0.1%) serum concentrations and would not be expected to take place at the much higher serum levels found in angiogenic sites in vivo. This conundrum can be resolved by recalling VEGF’s original function, that of an extremely potent vascular permeability factor (VPF). In vivo VPF/VEGF increases microvascular permeability such that whole plasma leaks into the tissues where it undergoes clotting by tissue factor that is expressed on tumor and host connective tissue cells to deposit fibrin and generate serum. By providing tissue support and by reprogramming the gene expression patterns of cells locally, fibrin and serum can together account for the formation of vascular connective tissue stroma. In sum, by increasing vascular permeability, VPF/VEGF triggers the “wound healing response,” setting in motion a fundamental pathophysiological process that induces the mature stroma that is found not only in healing wounds but also in solid tumors and chronic inflammatory diseases. Once initiated by increased vascular permeability, this response may be difficult to impede, perhaps contributing to the limited success of anti-VEGF therapies in treating cancer.
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影响因子：
3.1
作者：
Feng, D;Nagy, JA;Dvorak, HF
通讯作者：
Dvorak, HF
DOI：
10.1084/jem.180.3.1141
发表时间：
1994-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Detmar M;Brown LF;Claffey KP;Yeo KT;Kocher O;Jackman RW;Berse B;Dvorak HF
通讯作者：
Dvorak HF
影响因子：
56.9
作者：
DVORAK, HF;QUAY, SC;CARVALHO, AC
通讯作者：
CARVALHO, AC
影响因子：
9.8
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
通讯作者：
Brown PO
影响因子：
15.3
作者：
BROWN, LF;YEO, KT;BERSE, B;YEO, TK;SENGER, DR;DVORAK, HF;VANDEWATER, L
通讯作者：
VANDEWATER, L