Jensen Lasse Dahl, Gyllenhaal Charlotte, Block Keith
Biomol Concepts. 2014 Jun;5(3):245-56. doi: 10.1515/bmc-2014-0009.
Daily rhythms of light/darkness, activity/rest and feeding/fasting are important in human physiology and their disruption (for example by frequent changes between day and night shifts) increases the risk of disease. Many of the diseases found to be associated with such disrupted circadian lifestyles, including cancer, cardiovascular diseases, metabolic disorders and neurological diseases, depend on pathological de-regulation of angiogenesis, suggesting that disrupting the circadian clock will impair the physiological regulation of angiogenesis leading to development and progression of these diseases. Today there is little known regarding circadian regulation of pathological angiogenesis but there is some evidence that supports both direct and indirect regulation of angiogenic factors by the cellular circadian clock machinery, as well as by circulating circadian factors, important for coordinating circadian rhythms in the organism. Through highlighting recent advances both in pre-clinical and clinical research on various diseases including cancer, cardiovascular disorders and obesity, we will here present an overview of the available knowledge on the importance of circadian regulation of angiogenesis and discuss how the circadian clock may provide alternative targets for pro- or anti-angiogenic therapy in the future.
光/暗、活动/休息以及进食/禁食的日常节律对人体生理至关重要,而这些节律的紊乱(例如昼夜轮班的频繁变动)会增加患病风险。许多被发现与这种昼夜节律紊乱的生活方式相关的疾病,包括癌症、心血管疾病、代谢紊乱和神经疾病,都依赖于血管生成的病理性失调,这表明扰乱生物钟会损害血管生成的生理调节,从而导致这些疾病的发生和发展。目前,关于病理性血管生成的昼夜节律调节知之甚少,但有一些证据支持细胞生物钟机制以及循环昼夜节律因子对血管生成因子的直接和间接调节,这些因子对于协调机体的昼夜节律很重要。通过强调包括癌症、心血管疾病和肥胖症在内的各种疾病在临床前和临床研究方面的最新进展,我们将在此概述关于血管生成昼夜节律调节重要性的现有知识,并讨论生物钟未来如何可能为促血管生成或抗血管生成治疗提供替代靶点。