Biomarkers for cardiovascular disease

A biomarker, cardiovascular technology, used in microarrays and diagnostic reagents, the treatment of subjects suffering from cardiovascular disease, the field of ischemic heart disease

Inactive Publication Date: 2011-01-12
ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this percutaneous and invasive procedure comes with considerable risks

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  • Biomarkers for cardiovascular disease
  • Biomarkers for cardiovascular disease
  • Biomarkers for cardiovascular disease

Examples

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Embodiment 1

[0209]Blood vessel regrowth by angiogenesis may constitute an attractive therapeutic strategy for critical limb ischemia and ischemic heart disease. We have identified new molecular pathways by which angiogenesis can be controlled in appropriate animal models and tested their ability to restore vascular function. By DNA chip microarray analysis, we identified 1160 differentially expressed clones associated with different stages of angiogenesis in mouse development. We then combined the complementary strengths of mouse and zebrafish genetic studies to identify among these genes a key selector gene for angiogenesis. Genes obtained from microarrays can be used (1) to obtain their zebrafish orthologs and to perform whole-mount in situ hybridization in fish embryos to identify their expression patterns, and (2) to identify their expression patterns in zebrafish Antisense morpholinos were used to knock down those genes specifically expressed in hemangioblasts and blood vessels. Ne...

Embodiment 2

[0229] Genes that are differentially expressed during embryonic and ischemic angiogenesis: in vitro studies in 3D matrigel arrays; in mammalian models of hindlimb ischemia and atherosclerosis (and plaque instability), tumor angiogenesis and In vivo studies in a mouse model of acute myocardial infarction.

[0230] To further select and define the specific roles of candidate genes during mammalian angiogenesis, gain-of-function and loss-of-function modifications can be utilized in in vitro models of angiogenesis using recombinant viral vector-mediated gene transfer and siRNA-induced gene silencing, Selected genes involved in the regulation of angiogenesis were analyzed, as identified by previous DNA-microarray analysis, QPCR studies, and WISH analysis in zebrafish, morpholine ring knockdown analysis in zebrafish development. We used a 3D Matrigel system as an in vitro angiogenesis model. Differentiation of modified EC and EPC cells in general, into which gain-of-function or los...

Embodiment 3

[0242] Confirmation of genes cited in various aspects of the invention in humans and experimental animal models

[0243] The present invention relates to compositions and methods for the diagnosis and prediction of cardiovascular disease by evaluating selected angiogenesis / angiogenesis genes, such as those previously identified by microarrays. In particular, the invention encompasses the use of specific gene expression profiles of circulating endothelial progenitor cells to diagnose cardiovascular disease and predict clinical outcome. The feasibility of the approach for this approach was evaluated and confirmed in human groups and in experimental animal models of cardiovascular disease.

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Abstract

The present invention relates to a method of diagnosis or prognosis of cardiovascular disease in a subject, said method comprising the steps of detecting the presence of activated endothelial progenitor cells (EPCs) in a sample of a circulation fluid of said subject. The invention further relates to biomarkers for diagnosis or prognosis of cardiovascular disease in a patient, said biomarker comprising the expression product of a gene the expression of which is regulated during vasculogenesis.

Description

technical field [0001] The present invention belongs to the field of diagnostics, and more specifically, to the field of diagnosis, prediction and treatment of cardiovascular diseases. The present invention relates to biomarkers for diagnosing and predicting cardiovascular disease in a patient, methods for diagnosing and predicting cardiovascular disease in a subject, kits for performing such methods, and microarrays and diagnostic reagents useful for such methods. In particular, the diagnosed cardiovascular disease relates to ischemic heart disease. The invention further relates to methods of treating subjects suffering from cardiovascular disease at increased risk and pharmaceutical compositions suitable for use in such methods of treatment. Background technique [0002] Ischemic heart diseases, characterized by a reduced blood supply to the heart, are the leading cause of morbidity and mortality in the Western world. The disease constitutes a major investment in healthc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2600/158C12Q2600/106C12Q1/6883C12Q2600/136A61P9/10
Inventor 亨利克斯·约翰内斯·迪凯尔
Owner ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
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