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Department of Cell Biology Faculty
Sybill Patan, M.D., Ph.D.
Department of Cell Biology, Box 5
Tel: (718) 270-1018 • Fax: (718) 270-1016
Intussusceptive Microvascular Growth (IMG)
I am working on a new concept of blood vessel formation and growth termed "intussusceptive microvascular growth" (IMG) whose existence and cellular mechanisms I have documented using in vivo video microscopy combined with the analysis and reconstruction of serial sections at the light- and electron microscopic levels.
IMG forms an alternative mechanism to the concept of endothelial sprouting. The vascular network expands based on the division of the vessel lumen which is achieved by the formation and insertion of interstitial- or intervascular tissue structures (ITSs, diameter > 2.5 mm) and tissue pillars or posts (diameter < 2.5 mm). I demonstrated the ubiquitous existence of IMG during embryonic development in the chorio-allantoic membrane and throughout the body of the embryo. I also showed that IMG is an important mechanism of adult (post-natal) angiogenesis as it occurs in tissue repair, recanalization of thrombotic lesions, after myocardial infarctions, and during myocardial ischemia(even in human patients), as well as in tumors.
I have started to identify the molecular regulators involved in promoting or inhibiting IMG, such as Angiopoietin-1, the corresponding Tie-2 and Tie-1 receptors, FGF-2, and Thromboxane A2. A second important part of IMG is the concept that during blood vessel formation non-endothelial cells (as fibroblast-like precursor (stem) cells or even tumor cells) are able to replace endothelial cells by invading the vessel wall from a peri-endothelial position. Subsequently, this means a shift of focus from endothelial proliferation (as it is proposed in the sprouting concept) to endothelial differentiation. In this respect we currently study the expression of endothelial-specific markers in non-endothelial peri-vascular cells in various pathologic settings, as development of malignancies (starting from benign precursor stages) and after myocardial infarctions.