Beth Israel Deaconess Medical Center, Inc.

Arie Horowitz

Michael Simons

Ruediger Volk

Rudiger Volk

The present invention provides tangible means and methods for stimulation of angiogenesis via enhanced endothelial expression of core proteins having a syndecan-4 cytoplasmic region intracellularly. The tangible means include a prepared DNA sequence fragment having separate and individual DNA sequenced portions coding for an heparan sulfate binding extracellular domain, a central transmembrane domain, and a cytoplasmic domain coding for the syndecan-4 polypeptide. The prepared DNA sequence unitary fragment may be delivered to endothelial cells in-situ, both under in-vivo and/or in-vitro conditions, using suitable expression vectors including plasmids and viruses. The resulting transfected endothelial cells overexpress heparan sulfate binding, core proteins; and the resulting overexpression of these proteoglycan entities causes stimulation of angiogenesis in-situ.

Stimulation of angiogenesis via enhanced endothelial expression of syndecan-4 core proteins

Stimulation of angiogenesis via enhanced endothelial expression of syndecan-4 core

The present invention provides a methodology and compositions for stimulating angiogenesis in-situ within viable cells, tissues and organs comprising endothelial cells. The methodology focuses upon and controls the phosphorylation of the 183rd amino acid residue, serine, within the cytoplasmic domain and intracellular tail of transmembrane syndecan-4 proteoglycans which are then positioned at and through the cellular membrane of viable endothelial cells. By intervening and maintaining the 183rd residue in a non-phosphorylated state, a consequential cascade of intracellular events is initiated which result in a stimulation of angiogenesis in-situ.

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Waltham, MA, United States of America

Arie Horowitz