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Series GSE37824 Query DataSets for GSE37824
Status Public on May 16, 2012
Title Evaluation of a novel clinical platform for cardiovascular drug development
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Objectives –To determine whether inflammation biomarkers can be used as indicators of therapeutic response, an exploratory study was performed to ascertain whether short term improvements in risk parameters will have measureable effects on a pre-defined panel of plaque inflammation biomarkers.
Methods and Results – Patients (n=121) with peripheral arterial disease were enrolled into one of three sub-studies based upon the presence of hypercholesterolemia, hypertension, or diabetes. Patients were randomized to 6 weeks of drug treatment vs. placebo and underwent catheter excision of atherosclerotic tissue from one extremity at baseline and the contralateral extremity after treatment. Simvastatin 40mg once daily reduced LDL-C by 43% (p<0.01), losartan 50mg once daily reduced diastolic blood pressure by 4 mm Hg (p=0.099), and pioglitazone 30mg once daily reduced serum glucose by 66mg/dL (p=0.008). Despite these effects, there were no consistent treatment effects on a large panel of plaque protein, RNA and lipid biomarkers.
Conclusions – Short term treatment with drugs that improve cardiovascular risk parameters did not result in a measureable reduction in the levels of peripheral arterial plaque inflammation biomarkers. Further studies are required to identify biomarkers that are sufficiently predictive to be used to identify drug candidates for testing in large cardiovascular outcome studies. (ClinicalTrials.gov: NCT00720577)
 
Overall design Human peripheral atherosclerosis plaque was extracted from lower extremities, and RNA, lipids and proteins extracted. RNA was analyzed in an Agilent two-color platform.
 
Contributor(s) Puig O, Dansky H, O'Neill E
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Submission date May 07, 2012
Last update date May 17, 2012
Contact name Oscar Puig
E-mail(s) oscar_puig@merck.com
Organization name Merck Research Laboratories
Department Molecular Profiling Research Informatics
Street address 126 East Lincoln Ave
City Rahway
State/province NJ
ZIP/Postal code 07065
Country USA
 
Platforms (1)
GPL4372 Rosetta/Merck Human 44k 1.1 microarray
Samples (249)
GSM927371 Simvastatin w0 Trt 1 week 0 68-001 R_SFA de-salt - no bad QC
GSM927372 Placebo w0 Trt 2 week 0 44-002 R_POP - no bad QC
GSM927373 Simvastatin w6 Trt 1 week 6 68-001 L_POP de-salt - no bad QC
Relations
BioProject PRJNA167021

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Supplementary data files not provided
Processed data included within Sample table

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