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Regulation of Angiogenesis and Blood Supply01:24

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Circadian angiogenesis.

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    Disrupting daily circadian rhythms can increase disease risk by impairing angiogenesis regulation. Understanding circadian control of angiogenesis offers potential new therapeutic targets for diseases like cancer and cardiovascular disorders.

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    Area of Science:

    • Physiology
    • Pathology
    • Chronobiology

    Background:

    • Daily rhythms are crucial for human physiology; disruptions increase disease risk.
    • Diseases linked to circadian disruption (cancer, cardiovascular, metabolic, neurological) often involve deregulated angiogenesis.
    • The link between circadian clock disruption and pathological angiogenesis is not well understood.

    Purpose of the Study:

    • To review current knowledge on circadian regulation of angiogenesis.
    • To highlight advances in pre-clinical and clinical research linking circadian disruption to angiogenesis in diseases.
    • To discuss the potential of the circadian clock as a therapeutic target for angiogenesis-related disorders.

    Main Methods:

    • Literature review of pre-clinical and clinical studies.
    • Analysis of research on cancer, cardiovascular disorders, and obesity.
    • Synthesis of evidence on direct and indirect regulation of angiogenic factors by circadian machinery.

    Main Results:

    • Circadian clock disruption impairs physiological regulation of angiogenesis.
    • Evidence suggests both direct and indirect regulation of angiogenic factors by cellular and circulating circadian factors.
    • Circadian regulation plays a role in the development and progression of angiogenesis-dependent diseases.

    Conclusions:

    • Circadian regulation is important for angiogenesis.
    • Circadian clock machinery and factors influence angiogenic processes.
    • Targeting the circadian clock may offer novel pro- or anti-angiogenic therapeutic strategies for various diseases.