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Role of melatonin in controlling angiogenesis under physiological and pathological conditions

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Abstract

Angiogenesis depends on proangiogenic and anti-angiogenic molecules that regulate endothelial cell proliferation and migration. Well-regulated angiogenesis plays a pivotal role in many physiological conditions such as reproduction and embryonic development, while abnormal angiogenesis is also the basis of a variety of pathological processes including tumor metastasis and atherosclerotic plaque formation. Melatonin has a variety of biological effects, including inhibition of tumor metastasis, stabilizing atherosclerotic plaques, and the regulation of seasonal reproductive rhythms, etc. During certain pathophysiological processes, melatonin exerts different functions depending on its ability to regulate angiogenesis. This review reveals that melatonin has different effects on neovascularization under different physiological and pathological conditions. In tumors, in age-related ocular diseases, and in a hypoxic environment, melatonin inhibits neovascularization in tissues, while in gastric ulcers, skin lesions, and some physiologic processes, it promotes angiogenesis. We also speculate that melatonin may inhibit the neovascularization in atherosclerotic plaques, thus preventing the initiation and development of atherosclerosis. Most studies suggest that these effects are related to the role of melatonin in regulating of vascular endothelial growth factor and its receptors, but the specific regulatory mechanisms remain disparate, which may lead to the differential effects of melatonin on angiogenesis under different conditions. In this review, we thus summarize some seemingly contradictory mechanisms by which melatonin controls angiogenesis under different pathological and physiological conditions, and urge that the regulatory mechanisms be further studied.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81827808 and 81870178)

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Authors and Affiliations

  1. Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China

    Qiang Ma & Yundai Chen

  2. Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas, 78229, USA

    Qiang Ma & Russel J. Reiter

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  1. Qiang Ma
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  2. Russel J. Reiter
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Ma, Q., Reiter, R.J. & Chen, Y. Role of melatonin in controlling angiogenesis under physiological and pathological conditions. Angiogenesis 23, 91–104 (2020). https://doi.org/10.1007/s10456-019-09689-7

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