National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Cell Adh Migr. 2009 Oct-Dec;3(4):322-7. doi: 10.4161/cam.3.4.9459. Epub 2009 Oct 3.
Despite its early discovery and high sequence homology to the other VEGF family members, the biological function of VEGF-B remained debatable for a long time, and VEGF-B has received little attention from the field thus far. Recently, we and others have found that (1) VEGF-B is a potent survival factor for different types of cells by inhibiting apoptosis via suppressing the expression of BH3-only protein and other apoptotic/cell death-related genes. (2) VEGF-B has a negligible role in inducing blood vessel growth in most organs. Instead, it is critically required for blood vessel survival. VEGF-B targeting inhibited pathological angiogenesis by abolishing blood vessel survival in different animal models. (3) Using different types of neuro-injury and neurodegenerative disease models, VEGF-B treatment protected endangered neurons from apoptosis without inducing undesired blood vessel growth or permeability. Thus, VEGF-B is the first member of the VEGF family that has a potent survival/anti-apoptotic effect, while lacking a general angiogenic activity. Our work thus advocates that the major function of VEGF-B is to act as a "survival", rather than an "angiogenic" factor and implicates a therapeutic potential of VEGF-B in treating different types of vascular and neurodegenerative diseases.
尽管 VEGF-B 很早就被发现，并且与其他 VEGF 家族成员具有高度的序列同源性，但它的生物学功能在很长一段时间内一直存在争议，到目前为止，VEGF-B 并没有受到该领域的太多关注。最近，我们和其他人发现：（1）VEGF-B 通过抑制 BH3 仅蛋白和其他凋亡/细胞死亡相关基因的表达来抑制细胞凋亡，从而成为不同类型细胞的有效存活因子。（2）VEGF-B 在大多数器官中诱导血管生长的作用微不足道，相反，它对于血管的存活至关重要。在不同的动物模型中，VEGF-B 靶向治疗通过消除血管的存活来抑制病理性血管生成。（3）使用不同类型的神经损伤和神经退行性疾病模型，VEGF-B 治疗可防止濒危神经元发生凋亡，而不会引起不必要的血管生长或通透性增加。因此，VEGF-B 是 VEGF 家族中第一个具有强大的存活/抗凋亡作用，而缺乏一般血管生成活性的成员。我们的工作表明，VEGF-B 的主要功能是作为一种“存活”而非“血管生成”因子，这暗示了 VEGF-B 在治疗不同类型的血管和神经退行性疾病中的治疗潜力。
