The Brigham and Women's Hospital, Inc.

Millennium Pharmaceuticals Limited

Other

California Institute of Technology

Genentech, Inc.

Millenium Pharmaceuticals, Inc.

Michael A Gimbrone, Jr

Dean A Falb

Michael P Bevilacqua

Brian Seed

Siegfried Stengelin

David J Anderson

Joffre B Baker

Hai U Wang

Caroline Alice Hebert

Guillermo Garcia-Cardena

Dennis Huszar

Michael J Donovan

Tucker Collins

Myron I Cybulsky

Katherine Galvin

M Elyse Wheeler

Martin S Obin

Arterial and venous smooth muscle cells are molecularly distinct from the earliest stages of angiogenesis through to adulthood. This distinction is revealed by expression on arterial cells (e.g., arterial endothelial cells, arterial smooth muscle cells) of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous cells are necessary for angiogenesis. Expression of EphrinB2 in arterial cells (e.g., arterial endothelial cells, arterial smooth muscle cells) can be used to advantage in methods for targeting agents and/or encoded polypeptides to arterial smooth muscle cells, altering angiogenesis, assessing the effect of agents on arterial smooth muscle cells, identifying arterial smooth muscle cells, isolating arterial smooth muscle cells and production of artificial vessels, for example.

Artery smooth muscle- and vein smooth muscle-specific proteins and uses therefor

The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease. Moreover, the present invention provides methods for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of cardiovascular disease, and for monitoring the efficacy of compounds in clinical trials. Additionally, the present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions.

Compositions and methods for the treatment and diagnosis of cardiovascular disease using fehd545 as a target

The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

Compositions and methods for the treatment and diagnosis of cardiovascular disease

The present invention is based on the generation and phenotypic characterization of transgenic knockout homozygous rchd534 mutant mice which display characteristic cardiovascular disease symptoms. Such transgenic knockout homozygous rchd534 mutant mice are useful models for the analysis and characterization of rchd534 protein involvement in development and homeostasis of the cardiovascular system and tissue-specific regulation of the TGF-&bgr; signaling pathways. Such transgenic mice may be used for screening compounds that may potentially useful for treating or preventing cardiovascular disease.

Compositions and methods for the treatment and diagnosis of cardiovascular disease using rchd534 as a target

Compositions and methods for the treatment and diagnosis of cardiovascular disease using fchd540 as a target

Compositions and methods for treatment and diagnosis of cardiovascular

Compositions and methods for the treatment and diagnosis of

The invention relates to novel endothelial cell-leukocyte adhesion molecules designated ATHERO-ELAM. ATHERO-ELAM molecules are expressed on cultured endothelial cells stimulated with bacterial LPS and selectively mediate the binding of monocytes to the endothelial cells. Monoclonal antibodies specific for ATHERO-ELAM bind to vascular endothelial cells involved in early atherosclerotic lesions, but not to vascular endothelial cells from uninvolved arterial tissue. ATHERO-ELAM and antibodies directed to ATHERO-ELAM may be used in identifying early atherosclerotic lesions and in treating and preventing atherosclerosis.

Mononuclear leukocyte directed endothelial adhesion molecule associated

A method is provided for selectively targeting a therapeutic agent to a site of activated endothelium by administering a pharmaceutical composition comprising a therapeutically effective amount of an E-selectin (formerly called ELAM-1) specific monoclonal antibody conjugated to a therapeutic agent. An immunoconjugate comprising an E-selectin specific monoclonal antibody and a therapeutic agent is also provided. A method is also provided for the treatment of a vascular smooth muscle cell proliferative disorder, vasculitis, inflammation, post-reperfusion injury, microbial infections, acute or chronic allograft rejection, and leukemia, as well as for the inhibition of metastatic spread of tumor cells, by administering a pharmaceutical composition comprising a therapeutically effective amount of an E-selectin antibody, or antibody fragment, either alone, or conjugated to a therapeutic agent.

Antibodies specific for E-selectin and the uses thereof

Growing community of inventors

Jamaica Plain, MA, United States of America

Michael A Gimbrone, Jr