editorial interplay between oxidative stress and ... · editorial interplay between oxidative...

EditorialInterplay between Oxidative Stress and Inflammation inCardiometabolic Syndrome

Aaron L. Sverdlov,1,2 Gemma A. Figtree,3 John D. Horowitz,1 and Doan T. M. Ngo1,2

1Basil Hetzel Institute, University of Adelaide, Woodville South, SA 5011, Australia2Boston University School of Medicine, Boston, MA 02118, USA3Kolling Institute, University of Sydney, St Leonards, NSW 2065, Australia

Correspondence should be addressed to Aaron L. Sverdlov; [email protected]

Received 31 May 2016; Accepted 1 June 2016

Copyright © 2016 Aaron L. Sverdlov et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Around 50–60% of adults in western countries are eitheroverweight or obese with more than 25% falling into theobese category [1]. The metabolic imbalance underlying obe-sity has fueled the prevalence of cardiometabolic syndrome—a constellation of interrelated risk factors ofmetabolic originsthat together promote the increased risk of cardiovasculardisease (CVD) and type II diabetes [2]. These are the majorcauses of morbidity, mortality, and sky-rocketing healthcarecosts in industrialized countries. Obesity is the hallmarkcomponent of cardiometabolic syndrome with other keycomponents being insulin resistance, hypertension, dys-lipidemia, and endothelial dysfunction. While each of theassociated conditions has an independent effect, their clus-tering has a synergistic effect, making the risk of developingcardiovascular disease greater. Obesity with the associatedcardiometabolic syndrome components has a direct effecton atherogenic dyslipidemia, elevated blood pressure, andelevated plasma glucose and promotes proinflammatory andprothrombotic states.

Cardiometabolic syndrome is associated with increasedoxidative stress; however, the source of reactive oxygenspecies (ROS) and their exact targets are not well under-stood. Oxidation products of different organic moleculesincluding lipids, proteins, and nucleic acids have been usedto demonstrate the presence of oxidative stress in patientswith cardiometabolic syndrome and CVD. Mitochondriahave been shown to be a major source and target of reactiveoxygen species in obesity-induced heart disease with conse-quences being impaired cardiac energetics, development of

left ventricular hypertrophy, and diastolic dysfunction [3].Angiotensin II-induced activation of NADPH oxidase alsoplays a role, with direct effects via redox posttranslationalmodifications of proteins within the caveolar compartment.The further downstream effects of ROS and redox regulationare mediated mostly by protein oxidative and nitrosativeposttranslational modifications of proteins [4].

Cardiometabolic syndrome has also been associated withthe presence of a number of inflammatory markers. Low-grade inflammation is a common manifestation and couldplay a role in the pathogenesis of obesity and cardiometabolicsyndrome and its sequelae. Dysregulation of adipose tissuebiology plays a potential role in the initiation of inflammatoryevents in obesity and cardiometabolic syndrome causingchronic inflammatory response characterized by abnormaladipokine production and the activation of several proin-flammatory signaling pathways, resulting in the induction ofseveral proinflammatory cytokines from adipose tissue thathave been suggested to play a role in pathogenesis of CVD.Furthermore, the dysregulation adipose tissue biology, medi-ated by increased redox stress and inflammation, adverselyaffects angiogenesis both locally and systemically [5], furthercontributing to the global impact of cardiometabolic syn-drome.

It is important to remember that cardiometabolic syn-drome frequently coexists with many other diseases, linkedby its high prevalence as well as commonalities in aetiologyor even causative contribution. A common nexus betweenmany of these disease states is the presence of endothelial

Hindawi Publishing CorporationMediators of InflammationVolume 2016, Article ID 8254590, 3 pageshttp://dx.doi.org/10.1155/2016/8254590

2 Mediators of Inflammation

dysfunction, mediated either by decreased synthesis andenhanced clearance or by impaired bioaction of nitric oxide.

Rheumatoid arthritis, a common autoimmune inflamma-tory connective tissue condition, has been associated withincreased incidence of CVD. In this issue, T. Dimitroulaset al. investigated the relationship between levels of sym-metric dimethylarginine (SDMA), an inactive congener ofasymmetrical dimethylarginine, a marker and mediator ofnitric oxide synthase inhibition, and inflammatory burdenand CVD risk factors in a cohort of rheumatoid diseasepatients. Interestingly, the authors have not found such anassociation, potentially related to the interacting effects ofantirheumatoid therapy, factors affecting kinetics of SDMAand potentially methodology for SDMAmeasurement.

Chronic kidney disease is another condition that isintimately linked with incidence of cardiometabolic syn-drome and CVD. Kidney disease can result from impairedcardiovascular function but also can in turn lead toworseningcardiac and vascular stiffening and fibrosis. A study by S.Rasic et al., in this issue, suggests that malondialdehyde(an oxidative stress marker) and matrix metalloproteinase-9(a marker/mediator of fibrosis) are significant predictors ofatherosclerosis in chronic kidney disease patients. A. Bakillahet al. looked at the levels of nitrosatively modified proteins inplasma of chronic kidney disease patients undergoing kidneytransplantation and found a reduction in nitrated apolipopro-tein A-I after transplantation, suggesting reduction in oxida-tive/nitrosative stress. In an animal model of cardiometabolicsyndrome induced in rats by coca cola drinking M. Otero-Losada et al. found induction of cardiac remodeling andrenal damage, associated with increase in proinflammatorycytokines, hypertriglyceridemia, and oxidative stress.

While obesity itself has been linked to increased oxidativestress and inflammation, there are many discrepancies invarious observational studies. In this issue, S. M. Lee et al.found urinary malondialdehyde and CRP to be positivelyassociated with visceral fat area in a cohort of moderatelyobese middle-aged men. On the other hand, weight loss hasbeen associated with beneficial cardiometabolic remodeling,but the exact processes that lead to this improvement inmetabolic and cardiovascular homeostasis are incompletelyunderstood. S. Karki et al. observed increased expression ofadipose tissue lipolytic genes following bariatric weight loss;these correlated with improvements in systemic markers oflipid and glucose metabolism, providing a potential insightinto mechanisms of beneficial effects of weight loss.

Obesity and associated sedentary lifestyle are associatedwith an alteration in a number of secreted metabolic modu-lators; the precise role of many of these is still poorly under-stood. Irisin is a hormone secreted from the skeletal muscleunder the control of PGC-1𝛼, a metabolic master-regulator.Irisin has been suggested to be a mediator of the beneficialeffect of exercise, leading to improvement of obesity and glu-cose homeostasis; however, some controversies regarding itsrole remain. M. Quinones et al. found no difference in irisinlevels with induction of obesity or manipulation of leptin lev-els in 2 rodent models, adding to the uncertainties regardingthe role and regulation of irisin in obesity.

Poor sleep quality has been linked to development ofCVD especially evident in those with disrupted sleep pat-terns, such as shift workers. T. Kanagasabai and C. I. Arderninvestigated the relationship between sleep quality and para-meters of oxidative stress and inflammation in a cross-sectional study. They found some mixed results, in generalsuggesting that fair quality sleepers have the most “optimal”inflammatory and oxidative profile.

Finally, high circulating levels of prothrombotic factorsmay play an important role in predisposing to prothromboticepisodes, which underlie cardiovascular events seen in obe-sity.This is further compounded by the increased incidence ofatrial fibrillation seen in obese subjects, which in itself confersa much higher thromboembolic risk. N. Procter et al. studiedthe effect of reduction in left atrial deformation, leading toblood stasis and ultimately thromboembolic events, in atrialfibrillation. The authors did not find a relationship betweenreduced left atrial deformation and measures of thromboem-bolic risk, inflammatory activation, or platelet reactivity.

This issue on the interplay of cardiometabolic syndrome,oxidative stress, and inflammation brings together insightsfrom a wide variety of research and disease fields. Thesestudies add to the collective body of knowledge regardingthe epidemiology, comorbidities, and mechanistic insightsunderlying cardiometabolic syndrome and its cardiovasculareffects. The overall complexity of the pathophysiology ofcardiometabolic syndrome makes these tasks difficult andoverwhelming and further studies frequently addmore ques-tions than they answer. Developments in redox biomarkersfor human application, currently lagging behind their inflam-matory counterparts, may assist in dissecting the interactionof oxidative stress and inflammation in a more personalizedfashion in the clinic and improve targeted therapeutic strate-gies. Increased understanding of the mechanistic processesunderpinning the development and progression of the car-diometabolic syndrome will allow us to begin to improveoutcomes from this syndrome which is a major contributorto mortality, morbidity, and rising healthcare costs in oursociety.

Aaron L. SverdlovGemma A. FigtreeJohn D. HorowitzDoan T. M. Ngo

References

[1] D. M. Thomas, M. Weedermann, B. F. Fuemmeler et al.,“Dynamic model predicting overweight, obesity, and extremeobesity prevalence trends,” Obesity, vol. 22, no. 2, pp. 590–597,2014.

[2] Y.-W. Park, S. Zhu, L. Palaniappan, S. Heshka, M. R. Carnethon,and S. B. Heymsfield, “The metabolic syndrome: prevalenceand associated risk factor findings in the US population fromthe Third National Health and Nutrition Examination Survey,1988–1994,” Archives of Internal Medicine, vol. 163, no. 4, pp.427–436, 2003.

[3] A. L. Sverdlov, A. Elezaby, F. Qin et al., “Mitochondrial reactiveoxygen species mediate cardiac structural, functional, andmitochondrial consequences of diet-induced metabolic heart

Mediators of Inflammation 3

disease,” Journal of the American Heart Association, vol. 5,Article ID e002555, 2016.

[4] H. H. Rasmussen, E. J. Hamilton, C.-C. Liu, and G. A. Figtree,“Reversible oxidative modification: implications for cardiovas-cular physiology and pathophysiology,” Trends in Cardiovascu-lar Medicine, vol. 20, no. 3, pp. 85–90, 2010.

[5] D. T. M. Ngo, M. G. Farb, R. Kikuchi et al., “Antiangio-genic actions of vascular endothelial growth factor-A165b, aninhibitory isoform of vascular endothelial growth factor-A, inhuman obesity,”Circulation, vol. 130, no. 13, pp. 1072–1080, 2014.

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

editorial interplay between oxidative stress and ... · editorial interplay between oxidative...

Documents