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Oxidative Stress in Cardiac Remodeling Post-Ischemia/Reperfusion: Friend or Foe?

  • Emna Abidi
  • Abdullah Kaplan
  • George W. Booz
  • Fouad A. Zouein
Chapter

Abstract

Acute coronary artery disease remains the leading cause of death in the USA and most westernized cultures. Notwithstanding the promising pharmacological and interventional advances in the treatment of ischemic heart and vascular diseases in the last three decades, the World Health Organization (WHO) estimates that 17.7 million people die yearly from cardiovascular diseases (CVD), representing 31% of all deaths worldwide. More than 75% of CVD deaths, among which 80% are due to heart attacks and strokes, occur in low-income and middle-income countries. Reperfusion following myocardial infarction (MI) is a gold standard intervention that is proven to be highly effective in preventing heart failure development and death. However, reactive oxygen species (ROS) mediated myocardial injury following reperfusion has gained immense attention given its adverse prognostic value. This chapter discusses the mechanisms behind reperfusion induced cardiac injury while focusing on myocardial ROS types, sources and adverse effect. It also highlights the successful mito-targeted antioxidant therapy and touches base on the paradoxal cardioprotective effects of ROS, all within the context of myocardial ischemia/reperfusion (I/R).

Abbreviations

WHO

World Health Organization

CVD

Cardiovascular disease

Ca2+

Calcium

ROS

Reactive Oxygen Species

I/R

Ischemia Reperfusion

I/RI

Ischemia-Reperfusion Injury

MI

Myocardial Infarction

CHD

Coronary Heart Disease

PCI

Percutaneous Coronary Intervention

CABG

Coronary Artery Bypass Grafting

ATP

Adenosine triphosphate

Na+

Sodium

mPTP

Mitochondrial Permeability Transition Pore

H+

Hydrogen ion

NCX

Na+/Ca2+-exchanger

PKC-δ

Protein Kinase C delta

PKC-ɛ

Protein Kinase C epsilon

PARP

poly (ADP-ribose) polymerase

O2

Superoxide anion

XO

Xanthine oxidase

NADPH

Nicotinamide Adenine Dinucleotide Phosphate

NOS

Oxidase Synthase

MPO

Myeloperoxidase

nNOS

neuronal NOS

eNOS

endothelial NOS

iNOS

inducible NOS

NO

Nitric Oxide

ONOO

peroxynitrite

BH4

tetrahydrobiopterin

H2O2

hydrogen peroxide

ETC

Electron Transport Chain

XDH

Xanthine dehydrogenase

IL-1

Interleukine 1

IL-6

Interleukine 6

TNF-α

Tumor Necrosis Factor alpha

PMNs

Polymorphonuclear Lukocytes

HIF-1α

Hypoxia-inducible factor 1-alpha

MIM

Mitochondrial Inner Membrane

MnSOD

Manganese Superoxide Dismutase

H2O2

Hydrogen peroxide

MAPKs

Mitogen-activated Protein Kinases

RAF-MEK

Rapidly Accelerated Fibrosarcoma- Mitogen-activated protein kinase kinase pathway

PI3K

PI-3 kinase

HMGB1

High-mobility box 1

TLRs

Toll-Like Receptors

NFκB

Nuclear factor kappa-light-chain-enhancer of activated B cells

PKA

Protein Kinase A

Akt/PKB

Protein kinase B

Bcl-2

B-cell lymphoma 2

MMPs

Matrix metalloproteinases

BK

Big Potassium channels

mitoKATP

Mitochondrial ATP-sensitive K+ channel

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, Faculty of MedicineAmerican University of BeirutBeirutLebanon
  2. 2.Department of Pharmacology and Toxicology, School of MedicineUniversity of Mississippi Medical CenterJacksonUSA

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