A Case Control Study of Resveratrol Effects in Coronary Artery Disease Patients With Metabolic Syndrome

April 30, 2017 updated by: Tehran University of Medical Sciences

Effects of Resveratrol on Crosstalk Between Canonical β-catenin/Wnt and FOXO Pathways in Coronary Artery Disease Patients With Metabolic Syndrome: A Case Control Study

The aim of this study is to explore the role of Canonical β-catenin/Wnt and forkhead box O (FOXO) pathways by means of investigating their target genes in coronary artery disease (CAD) pathogenesis and to examine the effects of resveratrol (RES) on these pathways in CAD patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Metabolic syndrome is a constellation of cardiovascular and metabolic risk factors including obesity, insulin resistance, hypertension and dyslipidemia. Coronary artery disease (CAD) is considerably linked with these risk factors. Oxidative stress has a major role in development of atherosclerosis that is believed as the most common pathologic process underlying CAD. The up-regulated gene-expression of free radical scavenging enzymes such as manganese superoxide dismutase (MnSOD) by members of the forkhead box O (FOXO) transcription factors is considered to be one of the paramount cell defensive mechanisms against oxidative damage. It is now well recognized that β-catenin binds to FOXOs during oxidative stress and acts as the pivotal mediator in canonical Wnt signaling, so that it translocates to the nucleus and interacts with the family of transcription factors T-cell factor/lymphoid enhancer factor (TCF/LEF), to regulate the expression of Wnt target genes. Recent evidence suggested that the canonical Wnt signaling plays a profound role in regulation of lipid metabolism and glucose homeostasis. Peroxisome proliferator-activated receptor delta (PPAR-δ) is one of the Wnt target genes which is believed to be operative in cardiometabolic protection. Interestingly, it has been demonstrated that impaired Wnt signaling pathway is contributed to inflammation, foam cell formation, and endothelial dysfunction which are recognized as atherosclerosis pathogenic factors. Resveratrol (RES) (3, 4´, 5 trihydroxystilbene), a natural polyphenol with antioxidant effects can be found in red grapes and its processed drinks (e.g. red wine), peanuts, pomegranates and mulberries.Increasing body of evidence suggest a protective role for RES against CAD, however the underlying mechanisms still remain to be elucidated. We perform this study on 10 metabolic syndrome patients with three-vessel CAD and 10 sex-aged matched (men with 40-55 years old) healthy subjects as controls. The effects of RES on β-Catenin, manganese superoxide dismutase (MnSOD), and peroxisome proliferator-activated receptor delta (PPAR-δ) expression are evaluated in peripheral blood mononuclear cells (PBMCs) of participants.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

-Three vessel coronary artery disease with metabolic syndrome based on WHO criteria

Exclusion Criteria:

  • Malignancy,
  • Myocardial infarction,
  • Unstable angina,
  • Previous coronary intervention,
  • Inflammatory diseases,
  • Diabetes,
  • Hypertension,
  • Endocrine disorders,
  • Other known chronic diseases,
  • Antioxidant therapy or vitamin supplements in the previous 12 months,
  • Smokers .

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CAD, Metabolic syndrome .

Arm1:coronary artery disease with metabolic syndrome . Intervention:Resveratrol (3, 4´, 5 trihydroxystilbene), 50 micromolar,12hour treatment .

Each experiment repeats three times .
Dietary supplement: Resveratrol (3, 4´, 5 trihydroxystilbene)
Resveratrol (RES) (3, 4´, 5 trihydroxystilbene)
EXPERIMENTAL: Healthy subjects .

Arm2:healthy subjects Intervention:Resveratrol (3, 4´, 5 trihydroxystilbene), 50 micromolar,12hour treatment .

Each experiment repeats three times .
Dietary supplement: Resveratrol (3, 4´, 5 trihydroxystilbene)
Resveratrol (RES) (3, 4´, 5 trihydroxystilbene)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative gene expression by real-time PCR (polymerase chain reaction)
Time Frame: Change from baseline after 12-hour treatment with resveratrol
PBMCs (2×106/well) are seeded in 96-well plates and undergo overnight incubation in humidified atmosphere at 37° C temperature with 5% CO2(carbon dioxide), then the medium is removed by centrifugation at 300g for 15 min and replaced with a fresh medium containing 50 micromolar resveratrol (dissolved in DMSO (Dimethyl sulfoxide)) for 12 hours. Then, RNA extraction, cDNA(complementary DNA) synthesis and real-time PCR are performed for β-catenin, MnSOD, and PPAR-delta genes .
Change from baseline after 12-hour treatment with resveratrol

Secondary Outcome Measures

Outcome Measure
Time Frame
MnSOD enzyme activity assay .
Time Frame: Change from baseline after 12-hour treatment with resveratrol
Change from baseline after 12-hour treatment with resveratrol
Total β-catenin protein measurement
Time Frame: Change from baseline after 12-hour treatment with resveratrol
Change from baseline after 12-hour treatment with resveratrol

Other Outcome Measures

Outcome Measure
Time Frame
PBMCs viability assay by MTT ( 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) test .
Time Frame: Change from baseline after 12 and 24-hour treatment with resveratrol
Change from baseline after 12 and 24-hour treatment with resveratrol

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tehran University of Medical Sciences

Investigators

  • Study Chair: Taghi Golmohammadi, PhD, Tehran University of Medical Sciences
  • Study Chair: Arash Hosseinnejad, MD-PhD, Tehran University of Medical Sciences
  • Study Director: Reza Meshkani, PhD, Tehran University of Medical Sciences
  • Study Director: Mahmoud Shirzad, MD, Tehran Heart Center,Tehran University of Medical Sciences
  • Principal Investigator: Mehrnoosh Shanaki Bavarsad, PhD student, Tehran University of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (ACTUAL)

August 1, 2014

Study Completion (ACTUAL)

December 1, 2014

Study Registration Dates

First Submitted

May 9, 2014

First Submitted That Met QC Criteria

May 9, 2014

First Posted (ESTIMATE)

May 13, 2014

Study Record Updates

Last Update Posted (ACTUAL)

May 2, 2017

Last Update Submitted That Met QC Criteria

April 30, 2017

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17001-30-01-91

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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