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

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: Coronary Artery Disease; Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Resveratrol (3, 4´, 5 trihydroxystilbene)

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

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Islamic Republic of Iran

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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)	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 .	Change from baseline after 12-hour treatment with resveratrol
Total β-catenin protein measurement	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 .	Change from baseline after 12 and 24-hour treatment with resveratrol

Collaborators and Investigators

• 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

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: Metabolic syndrome; Coronary artery disease; Resveratrol; Wnt signaling; MnSOD; β-catenin; FOXO
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease; Insulin Resistance; Hyperinsulinism; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Syndrome; Metabolic Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: 17001-30-01-91