The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch
Open accessAbstract
Aims/hypothesis Obesity is an independent risk factor for heart diseases but the underlying mechanism is not clear. This study examined cardiac contraction, oxidative stress, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and the myosin heavy chain (MHC) isoform switch in obese mice.Methods Mechanical properties were evaluated in ventricular myocytes from C57BL/6J lean and Lep/Lep obese mice (formerly known as ob/ob mice), including peak shortening (PS), time to 50 or 90% PS, time to 50 or 90% relengthening (TR50, TR90), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca2+ and its decay (tau). Oxidative stress, lipid peroxidation, protein damage and SERCA activity were assessed by glutathione/glutathione disulfide, malondialdehyde, protein carbonyl and 45Ca2+ uptake, respectively. NADPH oxidase was determined by immunoblotting.Results Myocytes from Lep/Lep mice displayed depressed PS and +/- dL/dt, prolonged TR50, TR90, elevated resting [Ca2+]i, prolonged tau, reduced contractile capacity at high stimulus frequencies and diminished responsiveness to extracellular Ca2+ compared with lean controls. Cardiac glutathione/glutathione disulfide was decreased whereas malondialdehyde, protein carbonyl, membrane p47(phox) and membrane gp91(phox) were increased in the Lep/Lep group. SERCA isoenzyme 2a was markedly modified by oxidation in Lep/Lep hearts and associated with decreased 45Ca2+ uptake. The MHC isozyme displayed a shift from the alpha to the beta isoform in Lep/Lep hearts. Short-term incubation of angiotensin II with myocytes mimicked the mechanical defects, SERCA oxidation and 45Ca2+ uptake seen in Lep/Lep myocytes. Incubation of the NADPH oxidase inhibitor apocynin with Lep/Lep myocytes alleviated contractile defects without reversing SERCA oxidation or activity.Conclusions/interpretation These data indicate that obesity-related cardiac defects may be related to NADPH oxidase activation, oxidative damage to SERCA and the MHC isozyme switch.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In ob/ob mice, cardiomyocyte contractile function is reduced and is associated with reduced calcium sensitivity and altered calcium transients (88, 207).”
From Cardiac remodeling in obesity (2008) · cites this paper as [207]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Increased oxidative stress in obesity and its impact on metabolic syndrome
Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., & Shimomura, I. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21625 · Cited by 5,508
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases
Cai, H., Griendling, K. K., & Harrison, D. G. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00233-5 · Cited by 687
S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide
Adachi, T. K., Weisbrod, R. M., Pimentel, D. R., Ying, J., Sharov, V. S., Schöneich, C., & Cohen, R. A. (2004) · Nature Medicine · doi:10.1038/nm1119 · Cited by 662
Stolk, J. N., Hiltermann, T. J. N., Dijkman, J. H., & Verhoeven, A. J. (1994) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.11.1.8018341 · Cited by 650
Touyz, R. M., Chen, X., Tabet, F., Yao, G., He, G., Quinn, M. T., Pagano, P. J., & Schiffrin, E. L. (2002) · Circulation Research · doi:10.1161/01.res.0000020404.01971.2f · Cited by 590
Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase
McClung, J. P., Roneker, C. A., Mu, W., Lisk, D. J., Langlais, P., Liu, F., & Lei, X. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308096101 · Cited by 536
Oxidative stress and protein aggregation during biological aging
Squier, T. C. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00139-5 · Cited by 519
Boudina, S., Sena, S., O’Neill, B. T., Tathireddy, P., Young, M. E., & Abel, E. D. (2005) · Circulation · doi:10.1161/circulationaha.105.554360 · Cited by 502 · cited 1×
“Reduced contractile capacity and prolonged duration of relaxation have been indicated in obesity and type 2 diabetes [2, 16].”
BackgroundMyocardial Gene Expression in Dilated Cardiomyopathy Treated with Beta-Blocking Agents
Lowes, B. D., Gilbert, E. M., Abraham, W. T., Minobe, W. A., Larrabee, P., Ferguson, D. A., Wolfel, E. E., Lindenfeld, J., Tsvetkova, T. O., Robertson, A. D., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012630 · Cited by 500
What Mechanisms Underlie Diastolic Dysfunction in Heart Failure?
Kass, D. A., Bronzwaer, J. G. F., & Paulus, W. J. (2004) · Circulation Research · doi:10.1161/01.res.0000129254.25507.d6 · Cited by 480
Dalle‐Donne, I., Scaloni, A., Giustarini, D., Cavarra, E., Tell, G., Lungarella, G., Colombo, R., Rossi, R., & Milzani, A. (2004) · Mass Spectrometry Reviews · doi:10.1002/mas.20006 · Cited by 461
Mazumder, P. K., O’Neill, B. T., Roberts, M. W., Buchanan, J., Yun, U. J., Cooksey, R. C., Boudina, S., & Abel, E. D. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2366 · Cited by 437
Li, J., & Shah, A. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110073200 · Cited by 390
Leptin and hyperleptinemia - from friend to foe for cardiovascular function
Ren, J. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1810001 · Cited by 305
Self-citationImpact of beta-myosin heavy chain expression on cardiac function during stress
Krenz, M., & Robbins, J. M. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.09.044 · Cited by 259
Eckel, R. H., Barouch, W. W., & Ershow, A. G. (2002) · Circulation · doi:10.1161/01.cir.0000017823.53114.4c · Cited by 257
Decreased Sarcoplasmic Reticulum Activity and Contractility in Diabetic db/db Mouse Heart
Belke, D. D., Swanson, E. A., & DILLMANN, W. H. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3201 · Cited by 255
Xu, F.-P., Chen, M.-S., Wang, Y.-Z., Yi, Q., Lin, S.-B., Chen, A. F., & Luo, J.-D. (2004) · Circulation · doi:10.1161/01.cir.0000140766.52771.6d · Cited by 234
Leptin, obesity, and respiratory function
O'Donnell, C. P., Tankersley, C. G., Polotsky, V. P., Schwartz, A. R., & Smith, P. L. (2000) · Respiration Physiology · doi:10.1016/s0034-5687(99)00111-5 · Cited by 233
AT 1 Blockade Prevents Glucose-Induced Cardiac Dysfunction in Ventricular Myocytes
Privratsky, J. R., Wold, L. E., Sowers, J. R., Quinn, M. T., & Ren, J. T. (2003) · Hypertension · doi:10.1161/01.hyp.0000082814.62655.85 · Cited by 222
Self-citationLeptin Attenuates Cardiac Contraction in Rat Ventricular Myocytes
Nickola, M. W., Wold, L. E., Colligan, P. B., Wang, G., Samson, W. K., & Ren, J. T. (2000) · Hypertension · doi:10.1161/01.hyp.36.4.501 · Cited by 185
Self-citationLeptin attenuates respiratory complications associated with the obese phenotype
Tankersley, C. G., O'Donnell, C. P., Daood, M. J., Watchko, J. F., Mitzner, W., Schwartz, A. R., & Smith, P. L. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.85.6.2261 · Cited by 178
Reiser, P. J., & Kline, W. O. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.274.3.h1048 · Cited by 156
Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice
Dong, F., Zhang, X., Yang, X., Esberg, L. B., Yang, H., Zhang, Z., Culver, B., & Ren, J. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06241 · Cited by 155
Self-citationLeptin, obesity and cardiovascular disease
Correia, M., & Haynes, W. G. (2004) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200403000-00010 · Cited by 153
Razeghi, P., Young, M. E., Cockrill, T. C., Frazier, O. H., & Taegtmeyer, H. (2002) · Circulation · doi:10.1161/01.cir.0000026392.80723.dc · Cited by 136
Blough, E. R., Rennie, E. R., Zhang, F., & Reiser, P. J. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0003 · Cited by 125
Li, S., Du, ., Dolence, E. K., Fang, C. X., Mayer, G. E., Ceylan‐Isik, A. F., LaCour, K. H., Yang, X., Wilbert, C. J., Sreejayan, N., et al. (2005) · Aging Cell · doi:10.1111/j.1474-9728.2005.00146.x · Cited by 122
Self-citationOxidized proteins as a marker of oxidative stress during coronary heart surgery
Pantke, U., Volk, T. J., Schmutzler, M., Kox, W. J., Sitte, N., & Grune, T. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00144-6 · Cited by 118
Impact of β-myosin heavy chain isoform expression on cross-bridge cycling kinetics
Rundell, V. L. M., Manaves, V., Martin, A. F., & de Tombe, P. P. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00407.2004 · Cited by 117
Uzun, H., Zengin, K., Taşkın, M., Aydın, S., Şimşek, G., & Darıyerli, N. (2004) · Obesity Surgery · doi:10.1381/096089204323093453 · Cited by 116
Katakam, P. V. G., Tulbert, C. D., Snipes, J. A., Erdös, B., Miller, A. W., & Busija, D. W. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00715.2004 · Cited by 114
Ren, J. T., Sowers, J. R., Walsh, M. F., & Brown, R. A. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.4.h1708 · Cited by 111
Self-citationOxygen Free Radicals and Excitation-Contraction Coupling
Goldhaber, J. I., & Qayyum, M. S. (2000) · Antioxidants and Redox Signaling · doi:10.1089/ars.2000.2.1-55 · Cited by 103
Mouse models of mitochondrial dysfunction and heart failure
Russell, L. K., Finck, B. N., & Kelly, D. J. (2004) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2004.10.010 · Cited by 98
Wold, L. E., Relling, D. P., Duan, J., Norby, F. L., & Ren, J. T. (2002) · Hypertension · doi:10.1161/hy0102.100777 · Cited by 97
Self-citationRegulation of intracellular Ca2+ in the heart during diabetes
Pierce, G. N. (1997) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00010-2 · Cited by 91
Yang, X., Palanichamy, K., Ontko, A. C., Rao, M. N. A., Fang, C. X., Ren, J. T., & Sreejayan, N. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.01.049 · Cited by 87
Self-citationBarouch, L. A. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00079-8 · Cited by 73
Rundell, V. L. M., Geenen, D. L., Buttrick, P. M., & de Tombe, P. P. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00049.2004 · Cited by 59
Minhas, K. M., Khan, S. A., Raju, S. V. Y., Phan, A. C., Gonzalez, D. R., Skaf, M. W., Lee, K., Tejani, A. D., Saliaris, A. P., Barouch, L. A., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.084566 · Cited by 59
Yan, L., Orr, W. C., & Sohal, R. S. (1998) · Analytical Biochemistry · doi:10.1006/abio.1998.2799 · Cited by 58
Carnes, C. A., Geisbuhler, T. P., & Reiser, P. J. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00439.2003 · Cited by 54
Husain, K. M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.06.058 · Cited by 48
Olsson, M. C., Palmer, B. M., Stauffer, B. L., Leinwand, L. A., & Moore, R. L. (2003) · Circulation Research · doi:10.1161/01.res.0000111521.40760.18 · Cited by 48
Sabbah, H. N. (2004) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2004.09.009 · Cited by 26
Gender differences in myosin heavy chain-β and phosphorylated phospholamban in diabetic rat hearts
Zhong, Y., Reiser, P. J., & Matlib, M. A. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00547.2003 · Cited by 20
Lessons from the leptin paradox in cardiac regulation – too much versus too little
Ren, J. T. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086678 · Cited by 10
Self-citation
Cited by
Sorted by citations
Myocardial Fatty Acid Metabolism in Health and Disease
Lopaschuk, G. D., Ussher, J. R., Folmes, C. D. L., Jaswal, J. S., & Stanley, W. C. (2010) · Physiological Reviews · doi:10.1152/physrev.00015.2009 · Cited by 2,228
Diabetic Cardiomyopathy Revisited
Boudina, S., & Abel, E. D. (2007) · Circulation · doi:10.1161/circulationaha.106.679597 · Cited by 1,543
Fu, S., Yang, L., Li, P., Hofmann, O., Dicker, L. H., Hide, W. A., Lin, X., Watkins, S. M., Ivanov, A. R., & Hotamışlıgil, G. S. (2011) · Nature · doi:10.1038/nature09968 · Cited by 1,045
Molecular mechanisms of diabetic cardiomyopathy
Bugger, H., & Abel, E. D. (2014) · Diabetologia · doi:10.1007/s00125-014-3171-6 · Cited by 903
Seravalle, G., & Grassi, G. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.05.013 · Cited by 909
Metadata
- Authors
- Li, S.-Y., Yang, X., Ceylan-Isik, A. F., Du, M., Sreejayan, N., & Ren, J.
- Affiliations
- University of Wyoming (US)
- Corresponding author
- Ren, J.
- Venue
- Diabetologia
- Published
- 2006-04-13
- Volume
- 49
- Issue
- 6
- Pages
- 1434-1446
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2149180473
- Cited by
- 187
- References
- 51
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 7 · 2015: 12 · 2014: 10 · 2013: 10 · 2012: 16
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association (7-00-RA-21)
- American Heart Association (0355521Z)
- Ohio State University
- Montana State University
- National Institutes of Health
- National Institute on Aging (R03AG021324, AG-21324, R03 AG21324, 1R03 AG21324-01, R03 AG21324-01, 1 R03 AG21324)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- cardiac contractile dysfunction, obesity, ob/ob mice, NADPH oxidase, oxidative stress, angiotensin II, apocynin, oxidative modification, ventricular myocytes, lipid peroxidation, protein carbonylation, glutathione, p47phox
- MeSH terms
- Calcium-Transporting ATPases, Animals, Endoplasmic Reticulum, Enzyme Activation, Glutathione, Homozygote, Male, Mice, Inbred C57BL, Mice, Obese, Myocardial Contraction, Sarcoplasmic Reticulum, Cell Culture Techniques, NADPH Oxidases, Glutathione Disulfide, Calcium Signaling, Leptin, Muscle Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
