Clinical trial NCT02137421: A Case Control Study of Resveratrol Effects in Coronary Artery Disease Patients With Metabolic Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Coronary Artery Disease
Keywords: Coronary artery disease
Metabolic syndrome
Resveratrol
β-catenin
Wnt signaling
FOXO
MnSOD
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2014-05-13
Enrollment: 20
Sex: MALE
Minimum age (years): 40
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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 .

Primary outcomes:
measure: Relative gene expression by real-time PCR (polymerase chain reaction)
timeFrame: Change from baseline after 12-hour treatment with resveratrol
Secondary outcomes:
measure: MnSOD enzyme activity assay .
timeFrame: Change from baseline after 12-hour treatment with resveratrol
measure: Total β-catenin protein measurement
timeFrame: Change from baseline after 12-hour treatment with resveratrol
Other outcomes:
measure: PBMCs viability assay by MTT ( 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) test .
timeFrame: Change from baseline after 12 and 24-hour treatment with resveratrol
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Islamic Republic of Iran
Study officials:
affiliation: Tehran University of Medical Sciences
name: Taghi Golmohammadi, PhD
role: STUDY_CHAIR
affiliation: Tehran University of Medical Sciences
name: Arash Hosseinnejad, MD-PhD
role: STUDY_CHAIR
affiliation: Tehran University of Medical Sciences
name: Reza Meshkani, PhD
role: STUDY_DIRECTOR
affiliation: Tehran Heart Center,Tehran University of Medical Sciences
name: Mahmoud Shirzad, MD
role: STUDY_DIRECTOR
affiliation: Tehran University of Medical Sciences
name: Mehrnoosh Shanaki Bavarsad, PhD student
role: PRINCIPAL_INVESTIGATOR
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