Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The general view is that an increase in vascular growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting. However, several recent studies showed that an increase in mitogenic stimuli can also lead to the arrest of angiogenesis. This is due to the existence of intrinsic signaling feedback loops and cell cycle checkpoints that work in synchrony to maintain a balance between endothelial proliferation and sprouting. This balance is tightly and effectively regulated during tissue growth and is often deregulated or impaired in disease. Most therapeutic strategies used so far to promote vascular growth simply increase mitogenic stimuli, without taking into account its deleterious effects on this balance and on vascular cells. Here, we review the main findings on the mechanisms controlling physiological vascular sprouting, proliferation, and senescence and how those mechanisms are often deregulated in acquired or congenital cardiovascular disease leading to a diverse range of pathologies. We also discuss alternative approaches to increase the effectiveness of pro-angiogenic therapies in cardiovascular regenerative medicine.

血管细胞增殖和迁移的治疗性调节对于有效抑制癌症中的血管生成或其在心血管疾病中的诱导是必不可少的。一般认为，血管生长因子水平的增加或有丝分裂刺激有利于血管生成，因为它会导致内皮增殖和发芽的增加。然而，最近的几项研究表明，有丝分裂刺激的增加也会导致血管生成的停滞。这是由于内在信号反馈回路和细胞周期检查点的存在，它们同步工作以维持内皮增殖和发芽之间的平衡。这种平衡在组织生长过程中受到严格有效的调节，并且在疾病中经常被解除调节或受损。迄今为止用于促进血管生长的大多数治疗策略只是增加促有丝分裂刺激，而没有考虑其对这种平衡和血管细胞的有害影响。在这里，我们回顾了关于控制生理性血管发芽、增殖和衰老的机制的主要发现，以及这些机制如何在获得性或先天性心血管疾病中经常失调，从而导致各种病理。我们还讨论了提高心血管再生医学中促血管生成疗法有效性的替代方法。和衰老以及这些机制如何在获得性或先天性心血管疾病中经常失调，从而导致各种病理。我们还讨论了提高心血管再生医学中促血管生成疗法有效性的替代方法。和衰老以及这些机制如何在获得性或先天性心血管疾病中经常失调，从而导致各种病理。我们还讨论了提高心血管再生医学中促血管生成疗法有效性的替代方法。