Compositions and methods for the treatment and diagnosis of cardiovascular disease

Abstract

The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, advanced atherosclerosis / plaque rupture, ischemia / reperfusion, hypertension, restenosis, cardiac calcification, allo / xenograft valvular calcifications, 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. Moreover, the present invention is further based in part 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-beta signaling pathways.

Description

[0001] This application is a continuation-in-part of application Ser. No. 08 / 870,434, filed Jun. 6, 1997, which is a continuation-in-part of co-pending application Ser. No.08 / 799,910, filed Feb. 13, 1997, which claims priority benefit under 35 U.S.C. .sctn.119(e) of provisional application Ser. No. 60 / 011,787, filed Feb. 16, 1996; and this application is a continuation-in-part of application Ser. No. 08 / 485,573, filed Jun. 7, 1995, which is a continuation-in-part of co-pending application Ser. No.08 / 386,844, filed Feb. 10, 1995, each of which is incorporated herein by reference in its entirety.1. INTRODUCTION[0002] 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, arterial inflammation, and aortic and valvular calcification. The present invention further relates to screening methods to identify compositions and their thera...

AI Technical Summary

Benefits of technology

This approach allows for the identification of specific targets for therapeutic intervention, improving diagnostic monitoring and treatment efficacy for cardiovascular diseases, including atherosclerosis, ischemia / reperfusion, and arterial inflammation, and provides a framework for rational drug design and clinical trial evaluation.

Problems solved by technology

Cardiovascular disease is a major health risk throughout the industrialized world.

Such plaques occlude the blood vessel concerned and thus restrict the flow of blood, resulting in ischemia.

Ischemia is a condition characterized by a lack of oxygen supply in tissues of organs due to inadequate perfusion.

Many medical interventions, such as the interruption of the flow of blood during bypass surgery, for example, also lead to ischemia.

Ischemia may occur in any organ, however, that is suffering a lack of oxygen supply.

The failure rate after these approaches due to restenosis, in which the occlusions recur and often become even worse, is extraordinarily high (30-50%).

Cardiac valve calcification often results in obstruction of blood flow, which eventually leads to valve replacement.

Calcific aortic valve stenosis constitutes a significant health problem in the elderly.

However, such approaches cannot identify the full panoply of gene products that are involved in the disease process, much less identify those which may serve as therapeutic targets for the diagnosis and treatment of various forms of cardiovascular disease.

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