Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Tulane Brain Institute, Tulane University, New Orleans, LA 70112, USA.
Biomolecules. 2023 Apr 20;13(4):702. doi: 10.3390/biom13040702.
Therapeutic angiogenesis has long been considered a viable treatment for vasculature disruptions, including cerebral vasculature diseases. One widely-discussed treatment method to increase angiogenesis is vascular endothelial growth factor (VEGF) A. In animal models, treatment with VEGFA proved beneficial, resulting in increased angiogenesis, increased neuronal density, and improved outcome. However, VEGFA administration in clinical trials has thus far failed to replicate the promising results seen in animal models. The lack of beneficial effects in humans and the difficulty in medicinal translation may be due in part to administration methods and VEGFA's ability to increase vascular permeability. One solution to mitigate the side effects of VEGFA may be found in the VEGFA isoforms. VEGFA is able to produce several different isoforms through alternative splicing. Each VEGFA isoform interacts differently with both the cellular components and the VEGF receptors. Because of the different biological effects elicited, VEGFA isoforms may hold promise as a tangible potential therapeutic for cerebrovascular diseases.
治疗性血管生成一直被认为是一种可行的治疗方法，可用于治疗血管紊乱，包括脑血管疾病。一种广泛讨论的增加血管生成的治疗方法是血管内皮生长因子 (VEGF) A。在动物模型中，VEGFA 的治疗被证明是有益的，导致血管生成增加、神经元密度增加和预后改善。然而，迄今为止，VEGFA 在临床试验中的给药并未复制出在动物模型中看到的有希望的结果。在人类中缺乏有益的效果和药物转化的困难部分可能是由于给药方法和 VEGFA 增加血管通透性的能力。减轻 VEGFA 副作用的一个解决方案可能在 VEGFA 同工型中找到。VEGFA 能够通过选择性剪接产生几种不同的同工型。每种 VEGFA 同工型与细胞成分和 VEGF 受体的相互作用方式不同。由于引起的不同生物学效应，VEGFA 同工型可能有望成为治疗脑血管疾病的一种有实际潜力的治疗方法。
