Cited by 270Pulmonary Hypertension Research and TreatmentsSirtuins and Resveratrol in MedicineNitric Oxide and Endothelin Effects

The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.

SIRT3-AMP-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction

Open access

Lai, Yen-Chun, Tabima, Diana M., Dube, John J., Hughan, Kara S., Vanderpool, Rebecca R., Goncharov, Dmitry A., St. Croix, Claudette M., Garcia-Ocaña, Adolfo, Goncharova, Elena A., Tofovic, Stevan P., Mora, Ana L., Gladwin, Mark T.·2016·Circulation

DOI 10.1161/circulationaha.115.018935PMC PMC4766041

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND: Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension. METHODS AND RESULTS: To evaluate the efficacy and mechanism of nitrite in metabolic syndrome associated with PH-HFpEF, we developed a 2-hit PH-HFpEF model in rats with multiple features of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined treatment of vascular endothelial growth factor receptor blocker SU5416. Chronic oral nitrite treatment improved hyperglycemia in obese ZSF1 rats by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling. The glucose-lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well. Skeletal muscle biopsies from humans with metabolic syndrome after 12 weeks of oral sodium nitrite and nitrate treatment (IND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase. Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH-HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase. CONCLUSIONS: These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease.

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

Crossref · 10.1161/circulationaha.115.018935

Cites

74 of 74 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase
Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
Reduced Expression of Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension
Giaid, A., & Saleh, D. M. (1995) · New England Journal of Medicine · doi:10.1056/nejm199507273330403 · Cited by 1,366
Characterization of the AMP-activated Protein Kinase Kinase from Rat Liver and Identification of Threonine 172 as the Major Site at Which It Phosphorylates AMP-activated Protein Kinase
Hawley, S. A., Davison, M., Woods, A., Davies, S. P., Beri, R. K., Carling, D., & Hardie, D. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27879 · Cited by 1,264
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
Lombard, D. B., Alt, F. W., Cheng, H.-L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-07 · Cited by 1,216
Adiponectin and Metabolic Syndrome
Matsuzawa, Y., Funahashi, T., Kihara, S., & Shimomura, I. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000099786.99623.ef · Cited by 1,203
Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite
Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.103523 · Cited by 1,078
The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
Koo, S., Flechner, L., Qi, L., Zhang, X., Screaton, R. A., Jeffries, S., Hedrick, S. A., Xu, W., Boussouar, F., Brindle, P. K., et al. (2005) · Nature · doi:10.1038/nature03967 · Cited by 1,026
Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension
Taraseviciene‐Stewart, L., Kasahara, Y., Alger, L., Hirth, P., Mahon, G. M., Waltenberger, J. L., Voelkel, N. F., & Tuder, R. M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0343com · Cited by 835
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome
Hirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.019 · Cited by 787
AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury
Russell, R. R., Li, J., Coven, D. L., Pypaert, M., Zechner, C., Palmeri, M., Giordano, F. J., Mu, J., Birnbaum, M. J., & Young, L. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19297 · Cited by 738
Exercise and Respiratory Training Improve Exercise Capacity and Quality of Life in Patients With Severe Chronic Pulmonary Hypertension
Mereles, D., Ehlken, N., Kreuscher, S., Ghofrani, S., Hoeper, M. M., Halank, M., Meyer, F. J., Karger, G., Buss, J., Juenger, J., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.618397 · Cited by 724
Sirtuin 3, a New Target of PGC-1α, Plays an Important Role in the Suppression of ROS and Mitochondrial Biogenesis
Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., & Chang, Y. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011707 · Cited by 718
5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle.
Kurth-Kraczek, E. J., Hirshman, M. F., Goodyear, L. J., & Winder, W. W. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1667 · Cited by 715
Strategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576 · cited 1×
“An increasing number of therapeutic approaches, which enhance NO generation and bioactivity, have been proposed over the past decade and include the administration of nitrite and nitrate.(13,14) Recent publications from our group and others have shown that nitrite exhibits therapeutic efficacy in mouse, rat, and sheep…”
Background
SIRT3, a human SIR2 homologue, is an NAD- dependent deacetylase localized to mitochondria
Onyango, P. O., Celic, I., McCaffery, J. M., Boeke, J. D., & Feinberg, A. P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222538099 · Cited by 573
Activation of AMP‐activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders
Viollet, B., Foretz, M., Guigas, B., Horman, S., Dentin, R., Bertrand, L., Hue, L., & Andréelli, F. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.108506 · Cited by 543
Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase
Duplain, H., Burcelin, R., Sartori, C., Cook, S., Egli, M., Lepori, M., Vollenweider, P., Pedrazzini, T., Nicod, P., Thorens, B., et al. (2001) · Circulation · doi:10.1161/01.cir.104.3.342 · Cited by 533
Lung Function Impairment and Metabolic Syndrome
Leone, N., Courbon, D., Thomas, F., Bean, K., Jégo, B., Leynaert, B., Guize, L., & Zureik, M. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200807-1195oc · Cited by 531
Exercise Training in Patients With Heart Failure and Preserved Ejection Fraction
Pandey, A., Parashar, A., Kumbhani, D. J., Agarwal, S. K., Garg, J., Kitzman, D. W., Levine, B. D., Drazner, M. H., & Berry, J. D. (2014) · Circulation Heart Failure · doi:10.1161/circheartfailure.114.001615 · Cited by 513
Mammalian TAK1 Activates Snf1 Protein Kinase in Yeast and Phosphorylates AMP-activated Protein Kinase in Vitro
Momcilovic, M., Hong, S. P., & Carlson, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604399200 · Cited by 504
Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin
Lund, S., Holman, G. D., Schmitz, O., & Pedersen, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.13.5817 · Cited by 492
Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle
Palacios, O. M., Carmona, J. J., Michan, S., Chen, K. Y., Manabe, Y., III, J. L. W., Goodyear, L. J., & Tong, Q. (2009) · Aging · doi:10.18632/aging.100075 · Cited by 487
Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production
Jing, E., Emanuelli, B., Hirschey, M. D., Boucher, J., Lee, K. Y., Lombard, D., Verdin, E. M., & Kahn, C. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111308108 · Cited by 469
Activation of AMP-Activated Protein Kinase by Metformin Improves Left Ventricular Function and Survival in Heart Failure
Gundewar, S., Calvert, J. W., Jha, S. K., Toedt‐Pingel, I., Ji, S. Y., Nunez, D. J., Ramachandran, A., Anaya-Cisneros, M., Tian, R., & Lefer, D. J. (2008) · Circulation Research · doi:10.1161/circresaha.108.190918 · Cited by 425
Pulmonary Arterial Hypertension: The Clinical Syndrome
Lai, Y.-C., Potoka, K. C., Champion, H. C., Mora, A. L., & Gladwin, M. T. (2014) · Circulation Research · doi:10.1161/circresaha.115.301146 · Cited by 402
AMPK inhibition in health and disease
Viollet, B., Horman, S., Leclerc, J., Lantier, L., Foretz, M., Billaud, M., Giri, S., & Andreelli, F. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.488215 · Cited by 383
Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice
Carlström, M., Larsen, F. J., Nyström, T., Hezel, M., Borniquel, S., Weitzberg, E., & Lundberg, J. O. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008872107 · Cited by 382
Pulmonary Arterial Hypertension Is Linked to Insulin Resistance and Reversed by Peroxisome Proliferator–Activated Receptor-γ Activation
Hansmann, G., Wagner, R. A., Schellong, S., Pérez, V. D. J., Urashima, T., Wang, L., Sheikh, A. Y., Suen, R. S., Stewart, D. J., & Rabinovitch, M. (2007) · Circulation · doi:10.1161/circulationaha.106.663120 · Cited by 367
Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction
Kitzman, D. W., Nicklas, B. J., Kraus, W. E., Lyles, M. F., Eggebeen, J., Morgan, T. M., & Haykowsky, M. J. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00004.2014 · Cited by 345
Myocardial Titin Hypophosphorylation Importantly Contributes to Heart Failure With Preserved Ejection Fraction in a Rat Metabolic Risk Model
Hamdani, N., Franssen, C., Lourenço, A. P., Falcão‐Pires, I., Fontoura, D., Leite, S., Plettig, L., López, B., Ottenheijm, C. A. C., Becher, P. M., et al. (2013) · Circulation Heart Failure · doi:10.1161/circheartfailure.113.000539 · Cited by 307
The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia
Fagan, K. A., Fouty, B., Tyler, R. C., Morris, K. G., Hepler, L. K., Sato, K., Cras, T. D. L., Abman, S. H., Weinberger, H. D., Huang, P. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci3862 · Cited by 306
Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects with Type 2 Diabetes
Sriwijitkamol, A., Coletta, D. K., Wajcberg, E., Balbontin, G. B., Reyna, S. M., Barrientes, J., Eagan, P. A., Jenkinson, C. P., Cersosimo, E., DeFronzo, R. A., et al. (2007) · Diabetes · doi:10.2337/db06-1119 · Cited by 304
Increased Malonyl-CoA Levels in Muscle From Obese and Type 2 Diabetic Subjects Lead to Decreased Fatty Acid Oxidation and Increased Lipogenesis; Thiazolidinedione Treatment Reverses These Defects
Bandyopadhyay, G. K., Yu, J. G., Ofrecio, J., & Olefsky, J. M. (2006) · Diabetes · doi:10.2337/db06-0062 · Cited by 291
Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction
Thenappan, T., Shah, S. J., Gomberg-Maitland, M., Collander, B., Vallakati, A., Shroff, P., & Rich, S. (2011) · Circulation Heart Failure · doi:10.1161/circheartfailure.110.958801 · Cited by 289
Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator
Hunter, C. J., Dejam, A., Blood, A. B., Shields, H., Kim-Shapiro, D. B., Machado, R. F., Tarekegn, S., Mulla, N., Hopper, A. O., Schechter, A. N., et al. (2004) · Nature Medicine · doi:10.1038/nm1109 · Cited by 281
Self-citation
Insulin resistance in pulmonary arterial hypertension
Zamanian, R. T., Hansmann, G., Snook, S., Lilienfeld, D. E., Rappaport, K., Reaven, G. M., Rabinovitch, M., & Doyle, R. L. (2008) · European Respiratory Journal · doi:10.1183/09031936.00000508 · Cited by 269
Nitric Oxide Increases Glucose Uptake Through a Mechanism That Is Distinct From the Insulin and Contraction Pathways in Rat Skeletal Muscle
Higaki, Y., Hirshman, M. F., FUJII, N. L., & Goodyear, L. J. (2001) · Diabetes · doi:10.2337/diabetes.50.2.241 · Cited by 254
Massive Pulmonary Edema and Death After Prostacyclin Infusion in a Patient With Pulmonary Veno-occlusive Disease
Palmer, S. M., Robinson, L. J., Wang, A., Gossage, J. R., Bashore, T. M., & Tapson, V. F. (1998) · CHEST Journal · doi:10.1378/chest.113.1.237 · Cited by 237
Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action
Varma, V., Yao-Borengasser, A., Rasouli, N., Nolen, G. T., Phanavanh, B., Starks, T., Gurley, C., Simpson, P., McGehee, R. E., Kern, P. A., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90885.2008 · Cited by 229
Adiponectin and Cardiovascular Disease
Shibata, R., Ouchi, N., & Murohara, T. (2009) · Circulation Journal · doi:10.1253/circj.cj-09-0057 · Cited by 214
Sirtuin 3 deficiency is associated with inhibited mitochondrial function and pulmonary arterial hypertension in rodents and humans
Paulin, R., Dromparis, P., Sutendra, G., Gurtu, V., Zervopoulos, S., Bowers, L., Haromy, A., Webster, L., Provencher, S., Bonnet, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.011 · Cited by 214
trans-(−)-ε-Viniferin Increases Mitochondrial Sirtuin 3 (SIRT3), Activates AMP-activated Protein Kinase (AMPK), and Protects Cells in Models of Huntington Disease
Fu, J., Jin, J., Cichewicz, R. H., Hageman, S. A., Ellis, T. K., Xiang, L., Peng, Q., Jiang, M., Arbez, N., Hotaling, K., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.382226 · Cited by 213
Leg glucose uptake during maximal dynamic exercise in humans
Katz, A., Broberg, S., Sahlin, K., & Wahren, J. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.1.e65 · Cited by 198
Nitrite Potently Inhibits Hypoxic and Inflammatory Pulmonary Arterial Hypertension and Smooth Muscle Proliferation via Xanthine Oxidoreductase–Dependent Nitric Oxide Generation
Zuckerbraun, B. S., Shiva, S., Ifedigbo, E., Mathier, M. A., Mollen, K. P., Rao, J., Bauer, P. M., Choi, J. J. W., Curtis, E., Choi, A. M. K., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.891077 · Cited by 192
Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle
Lira, V. A., Soltow, Q. A., Long, J. H. D., Betters, J. L., Sellman, J. E., & Criswell, D. S. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00045.2007 · Cited by 181
Prevalence and Risk Factors of Pulmonary Hypertension in Patients With Elevated Pulmonary Venous Pressure and Preserved Ejection Fraction
Leung, C. C., Moondra, V., Catherwood, E., & Andrus, B. W. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.02.039 · Cited by 180
Association of the metabolic syndrome with pulmonary venous hypertension
Robbins, I. M., Newman, J. H., Johnson, R. F., Hemnes, A. R., Fremont, R. D., Piana, R. N., Zhao, D. X., & Byrne, D. W. (2009) · Chest · doi:10.1378/chest.08-2008 · Cited by 171
Unrecognized glucose intolerance is common in pulmonary arterial hypertension
Pugh, M. E., Robbins, I. M., Rice, T. W., West, J. D., Newman, J. H., & Hemnes, A. R. (2011) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2011.02.016 · Cited by 154
SIRT3 is crucial for maintaining skeletal muscle insulin action and protects against severe insulin resistance in high-fat-fed mice
Lantier, L., Williams, A. S., Williams, I. M., Yang, K. K., Bracy, D. P., Goelzer, M., James, F. D., Gius, D., & Wasserman, D. H. (2015) · Diabetes · doi:10.2337/db14-1810 · Cited by 151
Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition
Yu, X., McCorkle, S. K., Wang, M., Lee, Y., Li, J., Saha, A. K., Unger, R. H., & Ruderman, N. B. (2004) · Diabetologia · doi:10.1007/s00125-004-1570-9 · Cited by 151
Skeletal Muscle Dysfunction in Idiopathic Pulmonary Arterial Hypertension
Batt, J. A. E., Ahmed, S. S., Correa, J., Bain, A. D., & Granton, J. T. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0506oc · Cited by 146
Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle
Raney, M. A., & Turcotte, L. P. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01282.2007 · Cited by 135
Pulmonary Hypertension in Heart Failure Preserved Ejection Fraction
Guazzi, M. (2014) · Circulation Heart Failure · doi:10.1161/circheartfailure.113.000823 · Cited by 125
Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertension
Agard, C., Rolli‐Derkinderen, M., de la Roque, E. D., Rio, M., Sagan, C., Savineau, J., Loirand, G., & Pacaud, P. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00445.x · Cited by 124
Dietary Nitrate Ameliorates Pulmonary Hypertension: Cytoprotective Role for Endothelial Nitric Oxide Synthase and Xanthine Oxidoreductase
Baliga, R. S., Milsom, A. B., Ghosh, S. M., Trinder, S. L., MacAllister, R. J., Ahluwalia, A., & Hobbs, A. J. (2012) · Circulation · doi:10.1161/circulationaha.112.100586 · Cited by 110
Unexplained Pulmonary Hypertension in Elderly Patients
Shapiro, B. P., McGoon, M. D., & Redfield, M. M. (2007) · CHEST Journal · doi:10.1378/chest.06-1571 · Cited by 107
Dietary nitrite improves insulin signaling through GLUT4 translocation
Jiang, H., Torregrossa, A. C., Potts, A., Pierini, D., Aranke, M., Garg, H. K., & Bryan, N. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.809 · Cited by 105
Bioavailability of sodium nitrite from an aqueous solution in healthy adults
Hunault, C. C., van Velzen, A. G., Sips, A. J. A. M., Schothorst, R. C., & Meulenbelt, J. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.06.865 · Cited by 102
Diagnosis and Treatment of Secondary (Non–Category 1) Pulmonary Hypertension
Rich, S., & Rabinovitch, M. (2008) · Circulation · doi:10.1161/circulationaha.107.723007 · Cited by 99
Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion
Pride, C. K., Mo, L., Quesnelle, K., Dagda, R. K., Murillo, D., Geary, L., Corey, C., Portella, R., Zharikov, S., St Croix, C., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvt224 · Cited by 97
Diabetic nephropathy and long-term treatment effects of rosiglitazone and enalapril in obese ZSF1 rats
Bilan, V. P., Salah, E., Bastacky, S., Jones, H. B., Mayers, R. M., Zinker, B. A., Poucher, S. M., & Tofovic, S. P. (2011) · Journal of Endocrinology · doi:10.1530/joe-11-0122 · Cited by 86
RENAL FUNCTION AND STRUCTURE IN DIABETIC, HYPERTENSIVE, OBESE ZDFxSHHF-HYBRID RATS
Tofovic, S. P., Kusaka, H., Kost, C. K., & Bastacky, S. (2000) · Renal Failure · doi:10.1081/jdi-100100882 · Cited by 80
Muscle contractile activity regulates Sirt3 protein expression in rat skeletal muscles
Hokari, F., Kawasaki, E., Sakai, A., Koshinaka, K., Sakuma, K., & Kawanaka, K. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00335.2009 · Cited by 76
Endothelium-dependent pulmonary artery responses in chronic heart failure: Influence of pulmonary hypertension
Porter, T. R., Taylor, D. O., Cycan, A., Fields, J., Bagley, C. W., Pandian, N. G., & Mohanty, P. K. (1993) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(93)90552-c · Cited by 76
The influence of basal nitric oxide activity on pulmonary vascular resistance in patients with congestive heart failure
Cooper, C. J., Jevnikar, F. W., Walsh, T., Dickinson, J., Mouhaffel, A., & Selwyn, A. P. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00400-7 · Cited by 71
Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3
Lin, L., Chen, K., Khalek, W. A., Ward, J. L., Yang, H., Chabi, B., Wrutniak-Cabello, C., & Tong, Q. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085636 · Cited by 67
Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat
Casey, D. B., Badejo, A. M., Dhaliwal, J. S., Murthy, S. N., Hyman, A. L., Nossaman, B. D., & Kadowitz, P. J. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00543.2008 · Cited by 61
Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study
Leite, S., Oliveira‐Pinto, J., Tavares-Silva, M., Abdellatif, M., Fontoura, D., Falcão‐Pires, I., Leite-Moreira, A. F., & Lourenço, A. P. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00076.2015 · Cited by 61
Association of NOS3 gene with metabolic syndrome in hypertensive patients
Fernández, M., Ruiz, R., Gonzalez, M., Ramírez‐Lorca, R., Couto, C., Ramos, A., Gutierrez-Tous, R., de Rivera, J. M. P. S., Ruiz, A., Grilo, A., et al. (2004) · Thrombosis and Haemostasis · doi:10.1160/th04-02-0103 · Cited by 55
Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension
Enache, I., Charles, A., Bouitbir, J., Favret, F., Zoll, J., METZGER, D., Oswald–Mammosser, M., Gény, B., & Charloux, A. (2012) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-012-1485-6 · Cited by 53
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Nebulized Sodium Nitrite (AIR001) Following Repeat-Dose Inhalation in Healthy Subjects
Rix, P. J., Vick, A., Attkins, N., Barker, G. E., Bott, A. W., Alcorn, H. W., Gladwin, M. T., Shiva, S., Bradley, S. P., Hussaini, A., et al. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-014-0201-y · Cited by 48
Harnessing the Nitrate–Nitrite–Nitric Oxide Pathway for Therapy of Heart Failure With Preserved Ejection Fraction
Vanderpool, R. R., & Gladwin, M. T. (2014) · Circulation · doi:10.1161/circulationaha.114.014149 · Cited by 30
Inorganic nitrite improves components of the metabolic syndrome independent of weight change in a murine model of obesity and insulin resistance
Singamsetty, S., Watanabe, Y., Guo, L., Corey, C. G., Wang, Y., Tejero, J., McVerry, B. J., Gladwin, M. T., Shiva, S., & O'Donnell, C. P. (2015) · The Journal of Physiology · doi:10.1113/jp270386 · Cited by 26

Flagged first, then by citations

Research works printed but not linked: 2

10.1267/THRO04080413 · DOI
Pflieger A, Potus F, Malenfant S, Breuils-Bonnet S, Provencher S, Bonnet S. Skeletal muscle metabolism defect in human pulmonary arterial hypertension. Am J Respir Crit Care Med. 2014;189:A2622.

Sorted by citations

Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction
Obokata, M., Reddy, Y. N. V., Pislaru, S. V., Melenovsky, V., & Borlaug, B. A. (2017) · Circulation · doi:10.1161/circulationaha.116.026807 · Cited by 1,179
Nitric oxide signaling in health and disease
Lundberg, J. O., & Weitzberg, E. (2022) · Cell · doi:10.1016/j.cell.2022.06.010 · Cited by 879
Research Priorities for Heart Failure With Preserved Ejection Fraction: National Heart, Lung, and Blood Institute Working Group Summary
Shah, S. J., Borlaug, B. A., Kitzman, D. W., McCulloch, A. D., Blaxall, B. C., Agarwal, R., Chirinos, J. A., Collins, S., Deo, R. C., Gladwin, M. T., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.041886 · Cited by 436
Cellular and molecular pathobiology of heart failure with preserved ejection fraction
Mishra, S., & Kass, D. A. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00480-6 · Cited by 437
Metabolic Effects of Dietary Nitrate in Health and Disease
Lundberg, J. O., Carlström, M., & Weitzberg, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.007 · Cited by 374

See all 270

Authors: Lai, Y.-C., Tabima, D. M., Dube, J. J., Hughan, K. S., Vanderpool, R. R., Goncharov, D. A., St. Croix, C. M., Garcia-Ocaña, A., Goncharova, E. A., Tofovic, S. P., Mora, A. L., & Gladwin, M. T.
Affiliations: University of Pittsburgh (US)
From Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (Y.-C.L., D.M.T., K.S.H., R.R.V., D.A.G., E.A.G., S.P.T., A.L.M., M.T.G.); Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA (J.J.D.); Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, University of Pittsburgh, Pittsburgh, PA (K.S.H.); Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA (C.M.St.C.); Diabetes, Obesity and...
ORCID: Lai, Yen-Chun
Tabima, Diana M.
Hughan, Kara S.
Vanderpool, Rebecca R.
Goncharov, Dmitry A.
Goncharova, Elena A.
Tofovic, Stevan P.
Mora, Ana L.
Gladwin, Mark T.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2016-02-23
Volume: 133
Issue: 8
Pages: 717-731
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.115.018935
PMC: PMC4766041
OpenAlex: W2274562896
Cited by: 270
References: 74
Citations by year: 2026: 15 · 2025: 20 · 2024: 26 · 2023: 25 · 2022: 26 · 2021: 24 · 2020: 31 · 2019: 21 · 2018: 37 · 2017: 26 · 2016: 17
FWCI: 30.09
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: University of Pittsburgh (UL1TR000005, UL1RR024153, RR024153)
Hemophilia Center of Western Pennsylvania (T32 HL110849)
National Institutes of Health (5t32dk007729-24, UL1TR000005, UL1-TR- 000005, RR024153, TR000005)
National Heart, Lung, and Blood Institute (R01HL096973, P01HL103455, K23HL124051, HL110849, R01HL113178, R01HL098032, T32HL110849)
National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK-007729, P30DK020541)
National Center for Research Resources (UL1RR024153)
National Center for Advancing Translational Sciences
Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD052892)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: pulmonary hypertension, heart failure with preserved ejection fraction, nitrite, nitrate, SIRT3, AMPK, metformin, hyperglycemia, metabolic syndrome, skeletal muscle, GLUT4, leptin receptor, SU5416, vascular remodeling, animal models
MeSH terms: Animals, Cells, Cultured, Enzyme Activation, Heart Failure, Humans, Hyperglycemia, Hypertension, Pulmonary, Male, Metformin, Rats, Zucker, Sodium Nitrite, Stroke Volume, Mice, Knockout, Muscle, Skeletal, Mice, Rats, AMP-Activated Protein Kinases, Sirtuin 3, Mice, 129 Strain

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

SIRT3-AMP-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks