Murugesan Velayutham

Murugesan Velayutham
University of Pittsburgh | Pitt · Department of Cardiothoracic Surgery

PhD

About

85
Publications
11,745
Reads
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2,185
Citations
Citations since 2017
22 Research Items
849 Citations
2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150
Introduction
Murugesan Velayutham currently works at the Department of Surgery, University of Pittsburgh. Murugesan does research in Biochemistry. Their current project is to study the molecular mechanisms involved in cardiovascular biology and cardio-immunology. Murugesan extensively uses electron paramagnetic resonance (EPR) spectroscopic technique in his projects to study the free radicals and oxidative stress in organs such as, heart, kideney, liver, and lung.
Additional affiliations
July 2017 - present
University of Pittsburgh
Position
  • Professor (Assistant)
Description
  • Assistant Professor

Publications

Publications (85)
Article
Air pollution accounts for more than 7 million premature deaths worldwide. Using ultrafine carbon black (CB) and ozone (O 3) as a model for an environmental co-exposure scenario, the dose response relationships in acute pulmonary injury and inflammation were determined by generating, characterizing, and comparing stable concentrations of CB aerosol...
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Background The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is...
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Oxidation of engineered nanomaterials during application in various industrial sectors can alter their toxicity. Oxidized nanomaterials also have widespread industrial and biomedical applications. In this study, we evaluated the cardiopulmonary hazard posed by these nanomaterials using oxidized carbon black (CB) nanoparticles (CBox) as a model part...
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Environmental inhalation exposures are inherently mixed (gases and particles), yet regulations are still based on single toxicant exposures. While the impacts of individual components of environmental pollution have received substantial attention, the impact of inhalation co-exposures is poorly understood. Here, we mechanistically investigated pulm...
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Alterations in viscosity of biological fluids and tissues play an important role in health and diseases. It has been demonstrated that the electron paramagnetic resonance (EPR) spectrum of a 13C-labeled trityl spin probe (13C-dFT) is highly sensitive to the local viscosity of its microenvironment. In the present study, we demonstrate that X-band (9...
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Alarmins, sequestered self-molecules containing damage-associated molecular patterns, are released during tissue injury to drive innate immune cell pro-inflammatory responses. Whether endogenous negative regulators controlling early immune responses are also released at the site of injury is poorly understood. Herein, we establish that the stromal...
Article
The rechargeable aqueous zinc-ion batteries (ZIBs) based on the Zn/MnO2 couple and mildly acidic electrolyte have emerged as promising large-scale energy storage systems. This work reports an in situ electrochemical activation approach to oxidizing MnS into an electrochemically derived oxide (MnS-EDO), which unlocks its potential as high-performanc...
Article
Primary graft dysfunction (PGD) is directly related to ischemia-reperfusion (I/R) injury and a major obstacle in lung transplantation (LTx). Nitrite ( N O 2 - ), which is reduced in vivo to form nitric oxide (NO), has recently emerged as an intrinsic signaling molecule with a prominent role in cytoprotection against I/R injury. Using a murine mo...
Article
Objective: Ex vivo lung perfusion creates a proinflammatory environment leading to deterioration in graft quality that may contribute to post-transplant graft dysfunction. Triptolide has been shown to have a therapeutic potential in various disease states because of its anti-inflammatory properties. On this basis, we investigated the impact of tri...
Article
Objective Delivery of the stromal cell-derived cytokine IL-33 protects allografts from rejection by acting on CD11c+ DC that facilitate the expansion of regulatory T cells (Treg). IL-33 administration also permits tolerance induction at doses of co-stimulatory blockade that fails on their own. Based on these data we hypothesized that IL-33-stimulat...
Article
Cytochrome b5 reductase (CYB5R) plays a central role in many diverse metabolic reactions by coupling NAD(P)H oxidation to reduction of proteins, such as cytochrome b5 (CYB5). Together, CYB5R and CYB5 transfer electrons to terminal oxidases, such as the mitochondrial amidoxime reducing component (mARC) or hemoglobin. Previous studies have demonstrat...
Article
Tissue damage and the impairment of regenerative processes by excessive reactive oxygen species (ROS) contributes to the pathogenesis of various diseases in soft tissues including diabetes, atherosclerosis, Parkinson's disease and myocardial ischemic/reperfusion injury. In this study, a thermally responsive injectable hydrogel poly(NIPAAm-co-VP-co-...
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Heat-shock factor-1 (HSF-1) is an important transcription factor that regulates pathogenesis of many human diseases through its extensive transcriptional regulation. Especially, it shows pleiotropic effects in human cancer, and hence it has recently received increased attention of cancer researchers. After myriad investigations on HSF-1, the field...
Article
Mechanisms underlying early inflammation and subsequent muscle repair after injury are typically described in terms of the coordinated action of numerous waves of immune cells. It is now emerging, however, that a complex network of leukocyte- and stromal cell-derived cytokines orchestrate the early infiltration and function of pro-inflammatory leuk...
Article
Modified LDL uptake by macrophages lead to formation of foam cells is an early event in atherosclerosis. Recent studies have suggested that macrophage polarization contributes to the progression of atherosclerosis. In this report, we investigated the hypothesis that macrophage polarization differentially affects modified LDL uptake and subsequent f...
Article
Objectives: Modified LDL uptake by macrophages (MΦ) leading to foam cell formation is an early event in atherosclerosis. Recent studies suggest that MΦ polarization contributes to the progression of atherosclerosis. Therefore, we investigated the hypothesis that macrophage plasticity affects modified LDL uptake and subsequent foam cell formation. A...
Article
Sulfite is generated in vivo as a result of metabolism of sulfur containing amino acids methionine and cysteine. Sulfite is consumed as antioxidant/preservative in food, beverages and medications. We are also consuming it through exposure to major environmental pollutant - sulfur dioxide. The enzyme sulfite oxidase (SO) is responsible for the detox...
Article
Minocycline (MC) is a second-generation semi-synthetic analogue of tetracycline. MC has been used as an antibiotic and for the treatment of various diseases such as acne vulgaris, sexually transmitted diseases, and rheumatoid arthritis. MC is currently being explored in various clinical trials for the treatment of cardiovascular diseases such as st...
Article
Fcgamma receptors (FcγRs) are classified as activating (FcγRI, III, and IV) and inhibitory (FcγRII) receptors. Others and we have demonstrated that combined deficiency of all the three activating FcγRs (I, III and IV) in apolipoprotein E (apoE)-Fcγ chain double knockout (dKO) mice decreased atherosclerosis. In this report, we investigated the indep...
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In humans, sulfite is generated endogenously by the metabolism of sulfur containing amino acids such as methionine and cysteine. Sulfite is also formed from exposure to sulfur dioxide, one of the major environmental pollutants. Sulfite is used as an antioxidant and preservative in dried fruits, vegetables, and beverages such as wine. Sulfite is als...
Article
Introduction: Bicuspid aortic valve (BAV) is associated with an aortopathy that manifests as a dilatation of the proximal ascending aorta. The mechanisms of aneurysm formation in BAV patients are not completely understood. Our group established that medial smooth muscle cells (SMC) from aneurysmal BAV patients exhibit a weakened oxidative stress de...
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Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative...
Article
Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) dimi...
Article
The enzyme xanthine oxidoreductase (XOR) is an important source of oxygen free radicals and related postischemic injury. Xanthine dehydrogenase (XDH), the major form of XOR in tissues, can be converted to xanthine oxidase (XO) by oxidation of sulfhydryl residues or by proteolysis. The conversion of XDH to XO has been assumed to be required for radi...
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Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome) are protected aga...
Chapter
Myocardial infarction is the leading cause of heart failure. Current therapy for acute myocardial infarction is to reopen the occluded coronary artery and reperfuse the effected myocardium in an effort to salvage the heart muscle at risk. Through understanding the process of free radical generation in the ischemic and postischemic heart, salvage of...
Chapter
The main determinant of myocardial necrosis following an acute myocardial infarction (AMI) is duration of ischemia. Infarct size is a strong independent predictor of postinfarction mortality. Interventions able to protect the myocardium (myocardial protection) from death during an ischemic event are urgently needed. Myocardial injury associated wit...
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Over the last two decades, the role of NO in cellular processes and signaling has been extensively investigated. Under physiological and pathophysiological conditions, NO is produced primarily by specific NO synthase enzymes and also through the process of nitrite reduction. NO is an important biological signaling molecule in the vasculature and ti...
Article
In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. However, applications of EPRI have been limited by long projection acquisition times and the consequent fact that rapid gated EPRI was not po...
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The GTP binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O(2)()). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending isch...
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Increased levels of extracellular superoxide dismutase (ecSOD) induced by preconditioning or gene therapy protect the heart from ischemia/reperfusion injury. To elucidate the mechanism responsible for this action, we studied the effects of increased superoxide scavenging on nitric oxide (NO) bioavailability in a cardiac myocyte-specific ecSOD trans...
Data
1. EcSOD protein expression in isolated cardiomyocytes and whole heart from WT and ecSOD Tg mice detected by Western analysis (panel A); Representative Western-blots and quantitative analysis of eNOS expression in whole heart from WT and ecSOD Tg mice detected by Western analysis (n = 3, panel B). iNOS expression in whole heart from WT and ecSOD Tg...
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Aims The role of endothelial nitric oxide synthase (eNOS)/NO signalling is well documented in late ischaemic preconditioning (IPC); however, the role of eNOS and its activation in early IPC remains controversial. This study investigates the role of eNOS in early IPC and the signalling pathways and molecular interactions that regulate eNOS activatio...
Article
Reactive nitrogen/oxygen species (ROS/RNS) at low concentrations play an important role in regulating cell function, signaling, and immune response but in unregulated concentrations are detrimental to cell viability(1, 2). While living systems have evolved with endogenous and dietary antioxidant defense mechanisms to regulate ROS generation, ROS ar...
Article
The enzyme aldehyde oxidase (AO) is a member of the molybdenum hydroxylase family that includes xanthine oxidoreductase (XOR); however, its physiological substrates and functions remain unclear. Moreover, little is known about its role in cellular redox stress. Utilizing electron paramagnetic resonance spin trapping, we measured the role of AO in t...
Article
In vivo mapping of alterations in redox status is important for understanding organ specific pathology and disease. While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals, it does not provide anatomic visualization of the body. Proton MRI is well suited to provide anatomical visualization. We applied EPR/NMR c...
Article
In cells, mitochondria, endoplasmic reticulum, and peroxisomes are the major sources of reactive oxygen species (ROS) under physiological and pathophysiological conditions. Cytochrome c (cyt c) is known to participate in mitochondrial electron transport and has antioxidant and peroxidase activities. Under oxidative or nitrative stress, the peroxida...
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Heart failure is a common antecedent to atrial fibrillation; both heart failure and atrial fibrillation are associated with increased myocardial oxidative stress. Chronic canine heart failure reduces atrial action potential duration and atrial refractoriness. We hypothesized that inducible nitric oxide synthase 2 (NOS2) contributes to atrial oxidat...
Article
The ability of three dithiolethione cancer chemopreventives, oltipraz 1, anetholedithione (ADT) 2, 1,2-dithiole-3-thione (D3T) 3, and the major metabolite, 4, of 1, to induce the cytoprotective enzyme NQO1 in Hepa 1c1c7 cells and the inhibition of this induction by catalase are demonstrated. The ability of 1, 3, and 4 to form O(2)(*) has been repor...
Article
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Inducible nitric oxide synthase (iNOS) is an obligatory mediator of the late phase of ischemic preconditioning, but the mechanisms of its cardioprotective actions are unknown. In addition, it remains unclear whether sustained elevation of iNOS in myocytes provides chronic protection against ischemia/reperfusion injury. Constitutive overexpression o...
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Hypoxia induces various adoptive signaling in cells that can cause several physiological changes. In the present work, we have observed that exposure of bovine aortic endothelial cells (BAECs) to extreme hypoxia (1-5% O(2)) attenuates cellular respiration by a mechanism involving heat shock protein 90 (Hsp90) and endothelial nitric oxide (NO) synth...
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Many studies have demonstrated a biphasic effect of peroxynitrite in the myocardium, but few studies have investigated this biphasic effect on beta-adrenergic responsiveness and its dependence on contractile state. We have previously shown that high 3-morpholinosydnonimine (SIN-1) (source of peroxynitrite, 200 micromol/L) produced significant anti-...
Article
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Recent studies have demonstrated that increased expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 2a improves myocardial contractility and Ca2+ handling at baseline and in disease conditions, including myocardial ischemia-reperfusion (I/R). Conversely, it has also been reported that pharmacological inhibition of SERCA might improve pos...
Article
We have previously reported that H(2)O(2) is actively generated by cells at the wound site and that H(2)O(2)-driven redox signaling supports wound angiogenesis and healing. In this study, we have standardized a novel and effective electron paramagnetic resonance spectroscopy-based approach to assess the redox environment of the dermal wound site in...
Article
We investigated the role of iron deposition in atherosclerotic plaque instability using a novel approach of in vivo plaque characterization by a noninvasive, noncontrast magnetic resonance-based T2* measurement. This approach was validated using ex vivo plaque analyses to establish that T2* accurately reflects intraplaque iron composition. Iron cat...
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Peroxynitrite production increases during the pathogenesis of numerous cardiac disorders (e.g. heart failure). However, limited studies have investigated the mechanism through which peroxynitrite exerts anti-adrenergic effects. Thus, the purpose of this study is to investigate the contribution of phospholamban (PLB), a critical excitation-contracti...
Article
Tetrathiatriarylmethyl radicals are ideal spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging. The wide application of trityl radicals as biosensors of oxygen or other biological radicals was hampered by the lack of affordable large-scale syntheses. We report the large-scale synthesis of the Finland trityl radi...
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Altered nitric oxide (NO) biosynthesis is thought to play a role in the initiation and progression of atherosclerosis and may contribute to increased risk seen in other cardiovascular diseases. It is hypothesized that altered NO bioavailability may result from an increase in endogenous NO synthase (NOS) inhibitors, asymmetric dimethly araginine (AD...
Article
The major metabolite of the cancer chemopreventive agent oltipraz, a pyrrolopyrazine thione (PPD), has been shown to be a phase 2 enzyme inducer, an activity thought to be key to the cancer chemopreventive action of the parent compound. In cells, mitochondria are the major source of reactive oxygen species (ROS) and cytochrome c (cyt c) is known to...
Article
Aldehyde oxidase, a molybdoflavoenzyme that plays an important role in aldehyde biotransformation, requires oxygen as substrate and produces reduced oxygen species. However, little information is available regarding its importance in cellular redox stress. Therefore, studies were undertaken to characterize its superoxide and hydrogen peroxide produ...
Article
The major metabolite of the cancer chemopreventive oltipraz (1), a pyrrolopyrazine thione, 4, has been shown to be a phase two enzyme inducer, an activity thought to be a key to the cancer chemopreventive action of the parent compound. To understand the possible mechanism by which the metabolite acts as an inducer, a study of its potential to gener...
Article
The cancer chemopreventive actions of oltipraz, a member of a class of 1,2-dithiolethiones, have been primarily associated with the induction of phase 2 enzymes mediated by a 41bp enhancer element known as the anti-oxidant response element in the promoter regions of many phase 2 genes. It has been suggested that oxygen radical formation by oltipraz...
Article
The nitrone 5-carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO) was synthesized and characterized. Spin trapping of various radicals by AMPO was demonstrated for the first time by electron paramagnetic resonance (EPR) spectroscopy. The resulting spin adducts for each of these radicals gave unique spectral profiles. The hyperfine splitting constants for...
Article
Reperfusion of ischemic tissue is a common event in the treatment of heart attack and stroke. To study disease pathogenesis, methods are required to measure tissue perfusion and area at risk, as well as localized regions of injury. While histology can provide this information, its destructive nature precludes assessment of time course. Thus, there...
Article
The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic cells. It comprises one 20S catalytic complex (composed of four stacked rings of seven members) and two axially positioned 19S regulatory complexes (each containing about 18 subunits) that control substrate access to the catalytic chamber. In most cases, targeting to...
Article
A novel electron paramagnetic resonance (EPR)-based oxygen mapping procedure (EPROM) is applied to cartilage grown in a single-, hollow-fiber bioreactor (HFBR) system. Chondrocytes harvested from the sterna of 17-day-old chick embryos were inoculated into an HFBR and produced hyaline cartilage over a period of 4 weeks. Tissue oxygen maps were gener...
Article
Single crystal EPR of Mn(II)-doped [Co(H2O)6] (picsul)2·4H2O is studied in the temperature range of 123–300K. The angular variation of the zero-field transitio