Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 30 - 75 |
| Updated: | 4/17/2018 |
| Start Date: | May 2014 |
| End Date: | December 2018 |
Metabolic syndrome is a group of risk factors that increase a patient's likelihood for heart
attack, stroke and diabetes. Our research is aimed at understanding whether a drug,
resveratrol, commonly found in grapes and red wine, would have any benefit in reducing risk
factors in patients that have metabolic syndrome. Despite the use of aspirin and cholesterol
reducing medications, patients with metabolic syndrome still often have sticky platelets and
dysfunctional lipid profile. This is likely due to inflammation and high oxidative state. In
animal studies, this drug has reduced platelet stickiness and reduced oxidative stress.
However, the effects of this drug have not been researched in patients with metabolic
syndrome.
We are interested in studying whether the benefits of resveratrol described in animal models
can be translated to patients with metabolic syndrome who display high markers of oxidative
stress. We plan to give a short intervention of drug to patients and then determine if the
drug successfully:
1. Decreases the stickiness of platelets. This is important because sticky platelets are
more likely to form clot and contribute to plaque formation.
2. Reduce the circulating dysfunctional HDL. HDL and its protein and lipid constituents
help to inhibit oxidation, inflammation, activation of the blood vessel wall,
coagulation, and platelet aggregation. Dysfunctional HDL, as occurs in metabolic
syndrome patients, cannot properly protect against atherosclerosis.
attack, stroke and diabetes. Our research is aimed at understanding whether a drug,
resveratrol, commonly found in grapes and red wine, would have any benefit in reducing risk
factors in patients that have metabolic syndrome. Despite the use of aspirin and cholesterol
reducing medications, patients with metabolic syndrome still often have sticky platelets and
dysfunctional lipid profile. This is likely due to inflammation and high oxidative state. In
animal studies, this drug has reduced platelet stickiness and reduced oxidative stress.
However, the effects of this drug have not been researched in patients with metabolic
syndrome.
We are interested in studying whether the benefits of resveratrol described in animal models
can be translated to patients with metabolic syndrome who display high markers of oxidative
stress. We plan to give a short intervention of drug to patients and then determine if the
drug successfully:
1. Decreases the stickiness of platelets. This is important because sticky platelets are
more likely to form clot and contribute to plaque formation.
2. Reduce the circulating dysfunctional HDL. HDL and its protein and lipid constituents
help to inhibit oxidation, inflammation, activation of the blood vessel wall,
coagulation, and platelet aggregation. Dysfunctional HDL, as occurs in metabolic
syndrome patients, cannot properly protect against atherosclerosis.
Patients with metabolic syndrome are at increased risk of thrombotic complications, including
myocardial infarction and cardiovascular death. A meta-analysis of the studies assessing
cardiovascular risk in metabolic syndrome found a pooled relative risk for incident
cardiovascular events and death of 1.78. This propensity for thrombotic vascular events is in
the context of an increasing prevalence of metabolic syndrome, which in the 2003-2006 NHANES
Survey was found in 34% of the US population over the age of 20.
Two important contributors to the development of myocardial infarction and stroke are lipid
rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring
of these plaques. A growing body of evidence implicates oxidative modification of lipoprotein
lipids and apolipoproteins in the genesis of plaques. Platelet hyperactivity and the variable
response to antiplatelet therapy are features of the metabolic syndrome. Oxidative
modifications of LDL enhance activation of platelets, which themselves are oxidatively
stressed. Myeloperoxidase (MPO) initiates lipid peroxidation leading to dysfunctional HDL
production. Therefore, the hypotheses for the proposed investigations will address the
effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients
with metabolic syndrome. Resveratrol, as predicted from its structure, is an electron rich
molecule that can reduce free radicals. It has distinctive actions, however, that differ from
compounds that are conventionally referred to as "anti-oxidants". It has particular potency
as an inhibitor of radical formation by a number of peroxidases that likely participate in
the pathophysiology of metabolic syndrome. These include MPO, the peroxidase site of
prostaglandin H synthase-1 (PGHS-1; cyclooxygenase-1(COX-1)) and cytochrome c.
We will test the hypothesis that:
1. resveratrol reduces platelet activation in patients with metabolic syndrome. and
2. that resveratrol reduces the oxidative modification of HDL proteins in patients with
metabolic syndrome.
myocardial infarction and cardiovascular death. A meta-analysis of the studies assessing
cardiovascular risk in metabolic syndrome found a pooled relative risk for incident
cardiovascular events and death of 1.78. This propensity for thrombotic vascular events is in
the context of an increasing prevalence of metabolic syndrome, which in the 2003-2006 NHANES
Survey was found in 34% of the US population over the age of 20.
Two important contributors to the development of myocardial infarction and stroke are lipid
rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring
of these plaques. A growing body of evidence implicates oxidative modification of lipoprotein
lipids and apolipoproteins in the genesis of plaques. Platelet hyperactivity and the variable
response to antiplatelet therapy are features of the metabolic syndrome. Oxidative
modifications of LDL enhance activation of platelets, which themselves are oxidatively
stressed. Myeloperoxidase (MPO) initiates lipid peroxidation leading to dysfunctional HDL
production. Therefore, the hypotheses for the proposed investigations will address the
effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients
with metabolic syndrome. Resveratrol, as predicted from its structure, is an electron rich
molecule that can reduce free radicals. It has distinctive actions, however, that differ from
compounds that are conventionally referred to as "anti-oxidants". It has particular potency
as an inhibitor of radical formation by a number of peroxidases that likely participate in
the pathophysiology of metabolic syndrome. These include MPO, the peroxidase site of
prostaglandin H synthase-1 (PGHS-1; cyclooxygenase-1(COX-1)) and cytochrome c.
We will test the hypothesis that:
1. resveratrol reduces platelet activation in patients with metabolic syndrome. and
2. that resveratrol reduces the oxidative modification of HDL proteins in patients with
metabolic syndrome.
Inclusion Criteria:
- Metabolic Syndrome
Exclusion Criteria:
- Evidence of coronary artery disease
- Indication for use of aspirin for secondary prevention of thrombotic events
- Use of non-steroidal anti-inflammatory drugs or anti-platelet agents
- Pregnancy
- Patients with history of bleeding or gastrointestinal ulcers
- Patients with major illnesses such as ongoing malignancies, infections, cirrhosis
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