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  • Research Summary of Thomas Adair, Ph.D.

    Regulation of Angiogenesis

    The problem

    Angiogenic therapies provide a potential to conquer cancer, heart diseases, and more than 70 of life's most threatening medical conditions. The lives of at least one billion people worldwide could be improved with angiogenic therapy, according to the Angiogenesis Foundation (www.angio.org/). Despite the large number of diseases, there are few medicines or drugs that can be given to patients to control blood vessel growth.

    All tissues of the body require a continuous supply of oxygen to burn metabolic substrates that are needed for energy. Oxygen is conducted to these tissues by blood capillaries: more capillaries can improve tissue oxygenation and thus enhance energy production; fewer capillaries can lead to hypoxia and even anoxia in the tissues. This means that angiogenic therapies designed to control the growth and regression of blood capillaries can be used to improve the survival of poorly perfused tissues that are essential to the body (heart, brain, skeletal muscle, etc.) and to rid the body of unwanted tissues (tumors).

    Benefits to humans

    If we could control the growth of blood vessels, we would increase blood vessel growth in infarcted areas of the heart following a heart attack, skin grafts and wounds, especially burn wounds. We would also decrease blood vessel growth to prevent retrolental fibroplasias, where too much angiogenesis leads to blindness in infants; rheumatoid arthritis, where capillaries can erode the cartilage in the joints; diabetic retinopathies, where growth of new blood vessels often leads to blindness; psoriasis, where the excessive growth and shedding of the epidermis may depend on abnormal angiogenesis in the dermis; arteriosclerosis, where capillaries that grow in arterial plaques may bleed and contribute to sudden blockage of the coronary arteries; and cancer. This is especially true from cance because if we could inhibit angiogenesis in solid tumors, the cells in the tumor would literally starve to death.

    Current work

    We currently seek to answer the following questions: Why does exposure to a hypoxic environment stimulate the growth of microvessels from mouse left ventricle and at the same time inhibit microvessel growth from aortic rings in vitro? Why does adenosine seem to be required for normal growth of microvessels in the heart, but may actually inhibit microvessel growth from aortic explants? Can genetically engineered macrophages create a pro-angiogenic environment in ischemic tissues and thereby promote angiogenesis? Are epithelial Na+ Channel (ENaC) and Acide Sensing Ion Channel (ASIC) proteins required for normal angiogenesis?

    Summary of completed work

    Some of our previous studies are summarized in the following three publications:

    • Adair, T.H., W.J. Gay, and J-P. Montani. Growth regulation of the vascular system: Evidence for a metabolic hypothesis. AM. J. Physiol. 259: R393-R404, 1990.
    • Adair, T.H. Growth regulation of the vascular system: an emerging role for adenosine. Am. J. Physiol. 289: R283-R296, 2005.
    • Adair TH, Montani JP. Angiogenesis. Morgan & Claypool, 2010.
      (http://secure.aidcvt.com/mcp/ProdDetails.asp?ID=9781615043309&PG=1&Type=RLMa&PCS=MCP)