Mediterranean diet and cardioprotection: The role of nitrite, polyunsaturated fatty acids, and polyphenols

doi:10.1016/j.nut.2010.12.006

Nutrition

Volume 27, Issues 7–8, July–August 2011, Pages 733-744

https://doi.org/10.1016/j.nut.2010.12.006 Get rights and content

Abstract

The continually increasing rate of myocardial infarction (MI) in the Western world at least partly can be explained by a poor diet lacking in green vegetables, fruits, and fish and enriched in food that contains saturated fat. In contrast, a number of epidemiologic studies provide strong evidence highlighting the cardioprotective benefits of the Mediterranean diet enriched in green vegetables, fruits, fish, and grape wine. Regular consumption of these products leads to an accumulation of nitrate/nitrite/NO, polyunsaturated fatty acids (PUFA), and polyphenolic compounds, such as resveratrol, in the human body. Studies have confirmed that these constituents are bioactive exogenous mediators, which induce strong protection against MI. The aim of this review is to provide a critical, in-depth analysis of the cardioprotective pathways mediated by nitrite/NO, PUFA, and phenolic compounds of grape wines discovered in the recent years, including cross-talk between different mechanisms and compounds. Overall, these findings may facilitate the design and synthesis of novel therapeutic tools for the treatment of MI.

Introduction

Myocardial infarction (MI) remains a major clinical problem in the western world. Acute MI takes about 140,000 lives every year in the USA alone [1]. In general, MI is a consequence of a long ischemic insult, which initiates irreversible intracellular events including shortage of ATP supply, collapse of ionic homeostasis, and massive cardiomyocyte death. Although restoration of the blood flow through the ischemic zone is absolutely required for survival, most of the intracellular damage occurs during reperfusion. Thus, the problems associated with MI are largely attributed to ischemic-reperfusion (IR) injury [2]. IR injury results in impaired contractile function and depression of mitochondrial bioenergetics, as the consequences of imbalanced ionic homeostasis [3] and functional disturbances due to protein/lipid modifications [4].

Ischemic preconditioning (IPC) is an effective strategy to protect the model heart from MI. IPC usually comprises one or more short ischemic insults intercepted with reperfusion prior to a prolonged period of IR [4], [5]. Although the signaling mechanisms of IPC are still unclear, important roles for a number of associated events have been proposed; this includes, but is not limited to, modifications and translocations of intracellular kinases [6], activation of mitochondrial ATP sensitive potassium (mK_ATP) channels [6], and mild mitochondrial uncoupling [7]. However, clinical application of IPC is difficult. For this reason, another strategy in the development of MI treatments entails investigation of the mechanisms of IPC and development of pharmacologic tools to mimic these signaling pathways. Unfortunately, today not even a single U.S. Food and Drug Administration approved drug exists for the lowering of cardiac infarct size [8].

Based on several epidemiologic, clinical, and experimental studies, it has been established that certain types of diet may have beneficial effects for the cardiovascular (CV) system in general and be effective therapeutic tools for the prevention or treatment of MI [9], [10], [11], [12]. For example, the Mediterranean diet, which typically includes a bolus of green vegetables, fruits, fish, and grape wines, is associated with decreased concentrations of inflammatory markers such as C-reactive protein and interleukin-6 in MI survivors [13]. Although great success has been made in the accumulation of solid scientific background underlying these phenomena, the full mechanisms of protection are far from being elucidated. Recent studies show several components of the Mediterranean diet can trigger cardioprotection. This review focuses on a number of these components that have attracted attention over the past few years: 1) nitrite, 2) polyunsaturated fatty acids (PUFA), and 3) wine polyphenols. The interplay between these components is also discussed.

Section snippets

Accumulation of nitrate/nitrite in the human body: Impact of the Mediterranean diet

Although 80% of the basal plasma nitrite (NO₂⁻) level derives from oxidation of NO [14], reduction of nitrate (NO₃⁻) may also contribute to elevation of NO₂⁻ [15]. It has been reported that exogenous NO₃⁻ intake (10 mg/kg in humans) may increase plasma NO₂⁻ concentration up to four- to five-fold in 30 min [16]. Notably, plasma NO₂⁻ concentration was decreased by 50% in mice that were placed on a dieting lacking in both NO₃⁻/NO₂⁻ [17].

The largest dietary sources of NO₃⁻ for the human body

Cardioprotective efficacies of PUFA

A Mediterranean diet traditionally includes an abundance of vegetables and fish, both of which contain a substantial amount of diverse PUFA (ω-3, -6, -9). Epidemiologic studies demonstrate that there is a direct correlation between PUFA consumption (especially ω-3) and low levels of CV diseases in some populations [82], [83]. The scientific nomenclature of PUFA is well described (see, for review [84]), and will not be discussed in detail herein. Briefly, PUFA are divided into three classes

Cardioprotection by ω-6 derivatives

Although investigation of the cardioprotective events of PUFAs has been considerably shifted toward ω-3, it should be noted that several ω-6 AA derivatives, including 12(S)-hydroperoxyeicosatetraenoic acid [118], epoxyeicosatrienoic acids [119], [120], and 15-deoxy-Δ^12,14-prostaglandin J₂ [116], [117], have already been shown to induce protection against MI. It was reported that one of the mechanisms against MI afforded by 12(S)-hydroperoxyeicosatetraenoic acid may be through the activation of

Cardioprotection by phenolic components of red and white wines: Cross-talk with Sirtuins, caloric restriction, and IPC

About 500 years ago Alvise Cornaro, who died at age 102, explained his longevity and good health in the book “The Art of Living Long.” Based on his experiences, regular wine consumption and caloric restriction (CR) were two critical components of a long, healthy life.

Regular consumption of grape wine is an integral element of the Mediterranean diet. Epidemiologic studies have shown the beneficial effects of moderate consumption of wine on the CV system [10], [12]. Although the cardioprotective

Downstream mechanisms for SIRTs-mediated cardioprotection

Because SIRT1 has been shown to be activated by phenolic compounds [137], [154], [167], the downstream signaling cascades that account for the effects of this protein in cardioprotection are of great interest. SIRT1 deacetylates and activates eNOS, thereby increasing NO production [182], which is known to be protective in several CV diseases, including MI [26]. Furthermore, SIRT1 can be up-regulated and activated by NO [183], forming a positive feedback loop that enhances NO availability. Thus,

Concluding remarks: Possible interplay between NO₂⁻/NO, PUFAs, and polyphenols

The amount of food and the type of food we consume are two important issues that have a great impact on normal CV function. They may also determine the level of risk for CV pathology, including MI. Large portions of green vegetables, fruits, fish, and grape wine enrich the Mediterranean diet with nitrite, ω-3/ω-6 PUFAs, and polyphenols. This review describes the potential cardioprotective roles of these substances against MI, as well as a discussion of protective mechanisms. As highlighted in

Acknowledgments

We thank Paul S. Brookes, Keith W. Nehrke, Andrew P. Wojtovich, and William R. Urciuoli (Rochester) for stimulating discussions. This work was funded by a grant from National Institutes of Health to PSB (RO1-HL-071158).

References (215)

A.T. Turer et al.
Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy
Am J Cardiol
(2010)
M. Yokoyama et al.
Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis
Lancet
(2007)
P. Kleinbongard et al.
Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals
Free Radic Biol Med
(2003)
J.O. Lundberg et al.
Inorganic nitrate is a possible source for systemic generation of nitric oxide
Free Radic Biol Med
(2004)
N.J. Raat et al.
Dietary nitrate and nitrite modulate blood and organ nitrite and the cellular ischemic stress response
Free Radic Biol Med
(2009)
N.G. Hord et al.
Food sources of nitrates and nitrites: the physiologic context for potential health benefits
Am J Clin Nutr
(2009)
S.R. Tannenbaum et al.
The effect of nitrate intake on nitrite formation in human saliva
Food Cosmet Toxicol
(1976)
S.P. Jones et al.
The ubiquitous role of nitric oxide in cardioprotection
J Mol Cell Cardiol
(2006)
B. Gago et al.
Red wine-dependent reduction of nitrite to nitric oxide in the stomach
Free Radic Biol Med
(2007)
B.S. Rocha et al.
Dietary polyphenols generate nitric oxide from nitrite in the stomach and induce smooth muscle relaxation
Toxicology
(2009)

S. Basu et al.

Nitrite reductase activity of cytochrome c

J Biol Chem

(2008)

L.S. Burwell et al.

Cardioprotection by metabolic shut-down and gradual wake-up

J Mol Cell Cardiol

(2009)

S.M. Nadtochiy et al.

Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury

J Mol Cell Cardiol

(2007)

S.M. Nadtochiy et al.

In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine

J Mol Cell Cardiol

(2009)

S. Stewart et al.

Reversible blockade of electron transport with amobarbital at the onset of reperfusion attenuates cardiac injury

Transl Res

(2009)

J.E. Baker et al.

Nitrite confers protection against myocardial infarction: role of xanthine oxidoreductase, NADPH oxidase and K(ATP) channels

J Mol Cell Cardiol

(2007)

B.A. Freeman et al.

d’Ischia M. Nitro-fatty acid formation and signaling

J Biol Chem

(2008)

T. Cui et al.

Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators

J Biol Chem

(2006)

P.R. Baker et al.

Fatty acid transduction of nitric oxide signaling: multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator-activated receptor ligands

J Biol Chem

(2005)

C. Batthyany et al.

Reversible post-translational modification of proteins by nitrated fatty acids in vivo

J Biol Chem

(2006)

S.S. Sinha et al.

Myocardial protection by nitrite: evidence that this reperfusion therapeutic will not be lost in translation

Trends Cardiovasc Med

(2008)

K. Yamagishi et al.

Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study

J Am Coll Cardiol

(2008)

K. Nageswari et al.

Effect of saturated, omega-3 and omega-6 polyunsaturated fatty acids on myocardial infarction

J Nutr Biochem

(1999)

D. Mancardi et al.

Omega 3 has a beneficial effect on ischemia/reperfusion injury, but cannot reverse the effect of stressful forced exercise

Nutr Metab Cardiovasc Dis

(2009)

L. Demaison et al.

Influence of the phospholipid n-6/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia

Biochim Biophys Acta

(1994)

G.G. Abdukeyum et al.

Dietary (n-3) long-chain polyunsaturated fatty acids inhibit ischemia and reperfusion arrhythmias and infarction in rat heart not enhanced by ischemic preconditioning

J Nutr

(2008)

C. Wang et al.

n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review

Am J Clin Nutr

(2006)

C.J. Lavie et al.

Omega-3 polyunsaturated fatty acids and cardiovascular diseases

J Am Coll Cardiol

(2009)

B.C. Yang et al.

Long-term dietary fish oil supplementation protects against ischemia-reperfusion-induced myocardial dysfunction in isolated rat hearts

Am Heart J

(1993)

S. Hong et al.

Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation

J Biol Chem

(2003)

D. Lloyd-Jones et al.

Executive summary: heart disease and stroke statistics—2010 update: A report from the American Heart Association

Circulation

(2010)

L.H. Opie

Role of calcium and other ions in reperfusion injury

Cardiovasc Drugs Ther

(1991)

E. Murphy et al.

Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury

Physiol Rev

(2008)

C.E. Murry et al.

Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium

Circulation

(1986)

J.M. Downey et al.

Signaling pathways in ischemic preconditioning

Heart Fail Rev

(2007)

S.M. Nadtochiy et al.

Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotection

Biochem J

(2006)

R. Bolli et al.

Myocardial protection at a crossroads: the need for translation into clinical therapy

Circ Res

(2004)

Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico

Lancet

(1999)

G.R. Di et al.

Alcohol consumption and n-3 polyunsaturated fatty acids in healthy men and women from 3 European populations

Am J Clin Nutr

(2009)

I. Urquiaga et al.

Effect of Mediterranean and Occidental diets, and red wine, on plasma fatty acids in humans. An intervention study

Biol Res

(2004)

D.B. Panagiotakos et al.

Mediterranean diet and inflammatory response in myocardial infarction survivors

Int J Epidemiol

(2009)

J.O. Lundberg et al.

Nitrate, bacteria and human health

Nat Rev Microbiol

(2004)

O. Ozdestan et al.

Development of a cost-effective method for nitrate and nitrite determination in leafy plants and nitrate and nitrite contents of some green leafy vegetables grown in the Aegean region of Turkey

J Agric Food Chem

(2010)

A.D. Ologhobo et al.

Occurrence of nitrate, nitrite and volatile nitrosamines in certain feedstuffs and animal products

Nutr Health

(1996)

H.J. Kim et al.

Determination of nitrite in cured meats by ion-exclusion chromatography with electrochemical detection

J Assoc Off Anal Chem

(1990)

J.L. Bryant

Food, nutrition and the nitric oxide pathway: biochemistry and bioactivity

(2010)

C. Dezfulian et al.

Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics

Cardiovasc Res

(2007)

S.R. Tannenbaum et al.

Nitrite in human saliva. Its possible relationship to nitrosamine formation

J Natl Cancer Inst

(1974)

A.J. Webb et al.

Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite

Hypertension

(2008)

N. Benjamin et al.

Stomach NO synthesis

Nature

(1994)

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ReviewMediterranean diet and cardioprotection: The role of nitrite, polyunsaturated fatty acids, and polyphenols

Abstract

Introduction

Section snippets

Accumulation of nitrate/nitrite in the human body: Impact of the Mediterranean diet

Cardioprotective efficacies of PUFA

Cardioprotection by ω-6 derivatives

Cardioprotection by phenolic components of red and white wines: Cross-talk with Sirtuins, caloric restriction, and IPC

Downstream mechanisms for SIRTs-mediated cardioprotection

Concluding remarks: Possible interplay between NO2−/NO, PUFAs, and polyphenols

Acknowledgments

Am J Cardiol

Lancet

Free Radic Biol Med

Free Radic Biol Med

Free Radic Biol Med

Am J Clin Nutr

Food Cosmet Toxicol

J Mol Cell Cardiol

Free Radic Biol Med

Toxicology

J Biol Chem

J Mol Cell Cardiol

J Mol Cell Cardiol

J Mol Cell Cardiol

Transl Res

J Mol Cell Cardiol

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Trends Cardiovasc Med

J Am Coll Cardiol

J Nutr Biochem

Nutr Metab Cardiovasc Dis

Biochim Biophys Acta

J Nutr

Am J Clin Nutr

J Am Coll Cardiol

Am Heart J

J Biol Chem

Executive summary: heart disease and stroke statistics—2010 update: A report from the American Heart Association

Circulation

Role of calcium and other ions in reperfusion injury

Cardiovasc Drugs Ther

Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury

Physiol Rev

Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium

Circulation

Signaling pathways in ischemic preconditioning

Heart Fail Rev

Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotection

Biochem J

Myocardial protection at a crossroads: the need for translation into clinical therapy

Circ Res

Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico

Lancet

Alcohol consumption and n-3 polyunsaturated fatty acids in healthy men and women from 3 European populations

Am J Clin Nutr

Effect of Mediterranean and Occidental diets, and red wine, on plasma fatty acids in humans. An intervention study

Biol Res

Mediterranean diet and inflammatory response in myocardial infarction survivors

Int J Epidemiol

Nitrate, bacteria and human health

Nat Rev Microbiol

Development of a cost-effective method for nitrate and nitrite determination in leafy plants and nitrate and nitrite contents of some green leafy vegetables grown in the Aegean region of Turkey

J Agric Food Chem

Occurrence of nitrate, nitrite and volatile nitrosamines in certain feedstuffs and animal products

Nutr Health

Determination of nitrite in cured meats by ion-exclusion chromatography with electrochemical detection

J Assoc Off Anal Chem

Food, nutrition and the nitric oxide pathway: biochemistry and bioactivity

Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics

Cardiovasc Res

Nitrite in human saliva. Its possible relationship to nitrosamine formation

J Natl Cancer Inst

Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite

Hypertension

Stomach NO synthesis

Nature

Review
Mediterranean diet and cardioprotection: The role of nitrite, polyunsaturated fatty acids, and polyphenols

Concluding remarks: Possible interplay between NO₂⁻/NO, PUFAs, and polyphenols