Influence of cardiometabolic comorbidities on myocardial function, infarction, and cardioprotection: Role of cardiac redox signaling.


Andreadou I(1), Daiber A(2), Baxter GF(3), Brizzi MF(4), Di Lisa F(5), Kaludercic N(6), Lazou A(7), Varga ZV(8), Zuurbier CJ(9), Schulz R(10), Ferdinandy P(11).
Author information:
(1)Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: [Email]
(2)Department of Cardiology 1, Molecular Cardiology, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany; Partner Site Rhine-Main, German Center for Cardiovascular Research
(DZHK), Langenbeckstr, Germany. Electronic address: [Email]
(3)Division of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, United Kingdom.
(4)Department of Medical Sciences, University of Turin, Italy.
(5)Department of Biomedical Sciences, University of Padova, Italy; Neuroscience Institute, National Research Council of Italy
(CNR), Padova, Italy.
(6)Neuroscience Institute, National Research Council of Italy
(CNR), Padova, Italy.
(7)Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
(8)Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary.
(9)Laboratory of Experimental Intensive Care Anesthesiology, Department Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
(10)Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany. Electronic address: [Email]
(11)Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary.


The morbidity and mortality from cardiovascular diseases (CVD) remain high. Metabolic diseases such as obesity, hyperlipidemia, diabetes mellitus (DM), non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) as well as hypertension are the most common comorbidities in patients with CVD. These comorbidities result in increased myocardial oxidative stress, mainly from increased activity of nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, mitochondria as well as downregulation of antioxidant defense systems. Oxidative and nitrosative stress play an important role in ischemia/reperfusion injury and may account for increased susceptibility of the myocardium to infarction and myocardial dysfunction in the presence of the comorbidities. Thus, while early reperfusion represents the most favorable therapeutic strategy to prevent ischemia/reperfusion injury, redox therapeutic strategies may provide additive benefits, especially in patients with heart failure. While oxidative and nitrosative stress are harmful, controlled release of reactive oxygen species is however important for cardioprotective signaling. In this review we summarize the current data on the effect of hypertension and major cardiometabolic comorbidities such as obesity, hyperlipidemia, DM, NAFLD/NASH on cardiac redox homeostasis as well as on ischemia/reperfusion injury and cardioprotection. We also review and discuss the therapeutic interventions that may restore the redox imbalance in the diseased myocardium in the presence of these comorbidities.