Angiogenesis is a complex process describing the growth of new blood vessels from existing vasculature, and is triggered by local pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which increase the metabolism of endothelial cells (ECs). Angiogenesis takes part in various physiological conditions such as embryogenesis, placental growth, and in pathological conditions such as tumor growth, diabetic retinopathy, rheumatoid arthritis (RA) and ischemic diseases. Current therapies against excessive angiogenesis target vascular growth signaling. However, tumors often counteract these therapies through adaptive mechanisms, thus novel alternative anti-angiogenic strategies are needed. Targeting metabolism is a new anti-angiogenic paradigm, especially through the inhibition of energy metabolism and glycosylation, with the perspective of maintaining the delicate balance between the beneficial and deleterious effects of excessive angiogenesis in patients. Recent studies described a role for EC glycolysis and its main regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the regulation of angiogenesis, but only few studies are related to the role of the hexosamine biosynthesis pathway during angiogenesis. Glycosylation allows the formation of glycoproteins, glycolipids and proteoglycans and impacts many pathways. The addition of glycans to N-linked proteins is catalyzed by the enzymatic activity of N-acetylglucosaminyltransferases (GnTs), which regulates the glycosylation status of key angiogenic factors such as VEGF receptor 2 (VEGFR2) and Notch. In addition, glycan-galectin (Gal) interactions regulate vascular signaling programs and may contribute to tumor adaptations to anti-angiogenic strategies. Herein, we review novel pharmacological strategies targeting glycosylation, which could be used to decrease excessive angiogenesis in pathological conditions.

血管生成是一个复杂的过程，描述了来自现有脉管系统的新血管的生长，并由局部促血管生成因子（例如血管内皮生长因子（VEGF））触发，该因子会增加内皮细胞（EC）的代谢。血管生成参与各种生理条件，例如胚胎发生，胎盘生长，以及病理条件，例如肿瘤生长，糖尿病性视网膜病，类风湿关节炎（RA）和缺血性疾病。当前针对过度血管生成的疗法靶向血管生长信号。然而，肿瘤通常通过适应性机制抵消这些疗法，因此需要新颖的替代性抗血管生成策略。靶向代谢是一种新的抗血管生成范例，尤其是通过抑制能量代谢和糖基化，从维持过度血管生成的有益和有害作用之间的微妙平衡这一观点出发。最近的研究描述了EC糖酵解及其主要调节剂6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶3（PFKFB3）在调节血管生成中的作用，但是只有很少的研究与己糖胺生物合成的作用有关。血管生成过程中的通路。糖基化允许形成糖蛋白，糖脂和蛋白聚糖，并影响许多途径。聚糖向N-连接蛋白的加成反应是由N的酶促活性来催化的。6-双磷酸酶3（PFKFB3）在血管生成的调节中，但是只有很少的研究与六胺生物合成途径在血管生成中的作用有关。糖基化允许形成糖蛋白，糖脂和蛋白聚糖，并影响许多途径。聚糖向N-连接蛋白的加成反应是由N的酶促活性来催化的。6-双磷酸酶3（PFKFB3）在血管生成的调节中，但是只有很少的研究与六胺生物合成途径在血管生成中的作用有关。糖基化允许形成糖蛋白，糖脂和蛋白聚糖，并影响许多途径。聚糖向N-连接蛋白的加成反应是由N的酶促活性来催化的。N-乙酰氨基葡萄糖氨基转移酶（GnTs），可调节关键血管生成因子（例如VEGF受体2（VEGFR2）和Notch）的糖基化状态。另外，聚糖-半乳糖凝集素（Gal）相互作用调节血管信号程序，并可能有助于肿瘤适应抗血管生成策略。本文中，我们综述了针对糖基化的新型药理策略，该策略可用于减少病理条件下过度的血管生成。