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 accessAbstract
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.
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?
In the citing paper
“For example, obesity, hyperlipidemia, and systemic hypertension are common risk factors for Group I PAH as well as Group II (secondary to left-sided heart failure or PH-heart failure with preserved ejection fraction, HFpEF)[12,15,16], and are also a feature of HIV infection[17,18].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [15]
In the citing paper
“Delivered via intravenous, inhaled, or oral routes, nitrite reduces pulmonary and right heart pressures and prevents or reverses characteristic vascular remodeling and right ventricular hypertrophy (RVH) in several animal models of PAH[15,117,143,146–149].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [15]
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
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
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
Giaid, A., & Saleh, D. M. (1995) · New England Journal of Medicine · doi:10.1056/nejm199507273330403 · Cited by 1,366
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
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
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
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
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.
Cited by
Sorted by citations
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
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
Heart failure with preserved ejection fraction: from mechanisms to therapies
Lam, C. S. P., Voors, A. A., de Boer, R. A., Solomon, S. D., & van Veldhuisen, D. J. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy301 · Cited by 355
Lahm, T., Douglas, I. S., Archer, S. L., Bogaard, H. J., Chesler, N. C., Haddad, F., Hemnes, A. R., Kawut, S. M., Kline, J. A., Kolb, T. M., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201806-1160st · Cited by 353
Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction
Obokata, M., Reddy, Y. N. V., & Borlaug, B. A. (2019) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2018.12.034 · Cited by 324
Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy
Yu, W., Gao, B., Li, N., Wang, J., Qiu, C., Zhang, G., Liu, M., Zhang, R., Li, C., Ji, G., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.10.021 · Cited by 278
Nitric oxide signalling in kidney regulation and cardiometabolic health
Carlström, M. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-021-00429-z · Cited by 268
Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248
Vanderpool, R. R., Saul, M. I., Nouraie, M. S., Gladwin, M. T., & Simon, M. A. M. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.0128 · Cited by 228
Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging
Quan, Y., Xin, Y., Tian, G., Zhou, J., & Liu, X. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/9423593 · Cited by 226
Nesti, L., & Natali, A. (2017) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2017.04.009 · Cited by 211
Murine Models of Heart Failure With Preserved Ejection Fraction
Valero‐Muñoz, M., Backman, W., & Sam, F. (2017) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2017.07.013 · Cited by 217
Apostolova, N., Iannantuoni, F., Gruevska, A., Muntané, J., Rocha, M., & Víctor, V. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101517 · Cited by 208
The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure
Boucherat, O., Agrawal, V., Lawrie, A., & Bonnet, S. (2022) · Circulation Research · doi:10.1161/circresaha.121.319971 · Cited by 210
Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms
Chen, S., Gan, D., Lin, S., Zhong, Y., Chen, M., Zou, X., Shao, Z., & Xiao, G. (2022) · Theranostics · doi:10.7150/thno.71360 · Cited by 205
Zhang, J., Dong, J., Martin, M., He, M., Gongol, B., Marin, T., Chen, L., Shi, X., Yin, Y., Shang, F., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201712-2570oc · Cited by 190
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186
Self-citationThe Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 213
SIRT3: A New Regulator of Cardiovascular Diseases
Sun, W., Liu, C., Chen, Q., Liu, N., Yan, Y., & Liu, B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7293861 · Cited by 172
The glycolytic process in endothelial cells and its implications
Susan, W. S. L., & Shi, Y. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00647-y · Cited by 177
Borlaug, B. A., Melenovský, V., & Koepp, K. E. (2016) · Circulation Research · doi:10.1161/circresaha.116.309184 · Cited by 157
Dai, J., Zhou, Q., Chen, J., Rexius‐Hall, M. L., Rehman, J., & Zhou, G. (2018) · Nature Communications · doi:10.1038/s41467-018-06376-x · Cited by 149
Pulmonary Hypertension in HFpEF and HFrEF
Guazzi, M., Ghio, S., & Adir, Y. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.06.069 · Cited by 149
Sirtuins and Insulin Resistance
Zhou, S., Tang, X., & Chen, H. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00748 · Cited by 155
Xu, M., Xue, R., Lü, Y., Yong, S.-Y., Wu, Q., Cui, Y.-L., Zuo, X.-T., Yu, X., Zhao, M. F., & Zang, W. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy217 · Cited by 144
Lin, C., Chen, T.-L., Tseng, Y., Wu, G., Hsieh, M.-H., Lin, Y., & Chen, R. (2016) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2016.05.018 · Cited by 131
Epidemiology and pathogenesis of heart failure with preserved ejection fraction
Nair, N. (2020) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm.2020.04.154 · Cited by 142
Meng, G., Liu, J., Liu, S., Song, Q., Liu, L., Xie, L., Han, Y., & Ji, Y. H. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13861 · Cited by 124
Metabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart Disease
Ranchoux, B., Nadeau, V., Bourgeois, A., Provencher, S., Tremblay, È., Omura, J., Côté, N., Abu-Alhayja’a, R., Dumais, V., Nachbar, R. T., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314555 · Cited by 110
Macrophages in Heart Failure with Reduced versus Preserved Ejection Fraction
DeBerge, M., Shah, S. J., Wilsbacher, L. D., & Thorp, E. B. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.01.002 · Cited by 109
Lourenço, A. P., Leite-Moreira, A. F., Balligand, J., Bauersachs, J. K., Dawson, D. K., de Boer, R. A., Windt, L. J. D., Falcão‐Pires, I., Fontes‐Carvalho, R., Franz, S., et al. (2017) · European Journal of Heart Failure · doi:10.1002/ejhf.1059 · Cited by 109
Obesity Is Associated With Pulmonary Hypertension and Modifies Outcomes
Frank, R. C., Min, J., Abdelghany, M., Paniagua, S. M., Bhattacharya, R., Bhambhani, V., Pomerantsev, E. V., & Ho, J. E. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.014195 · Cited by 98
Polydatin protects cardiomyocytes against myocardial infarction injury by activating Sirt3
Zhang, M., Zhao, Z., Shen, M., Zhang, Y., Duan, J.-H., Guo, Y., Zhang, D., Hu, J., Lin, J. M., Man, W., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.09.003 · Cited by 96
Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence
Salvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Martino, A. D., Albanese, G., Marfella, R., Sardu, C., et al. (2021) · Biomolecules · doi:10.3390/biom11121834 · Cited by 99
Egnatchik, R. A., Brittain, E. L., Shah, A. T., Fares, W. H., Ford, H. J., Monahan, K., Kang, C., Kocurek, E. G., Shijun, Z., Luong, T., et al. (2016) · Pulmonary Circulation · doi:10.1086/690236 · Cited by 95
Ahluwalia, A., Gladwin, M., Coleman, G. D., Hord, N., Howard, G., Kim‐Shapiro, D. B., Lajous, M., Larsen, F. J., Lefer, D. J., McClure, L. A., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003402 · Cited by 92
Sunamura, S., Satoh, K., Kurosawa, R., Ohtsuki, T., Kikuchi, N., Al-Mamun, M. E., Shimizu, T., Ikeda, S., Suzuki, K., Satoh, T., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1721298115 · Cited by 93
Anti-obesity and anti-diabetic effects of nitrate and nitrite
Ghasemi, A., & Jeddi, S. (2017) · Nitric Oxide · doi:10.1016/j.niox.2017.08.003 · Cited by 92
Gheibi, S., Jeddi, S., Carlström, M., Gholami, H., & Ghasemi, A. (2018) · Nitric Oxide · doi:10.1016/j.niox.2018.02.002 · Cited by 90
Simon, M. A. M., Vanderpool, R. R., Nouraie, M. S., Bachman, T. N., White, P. M., Sugahara, M., Gorcsan, J., Parsley, E. L., & Gladwin, M. T. (2016) · JCI Insight · doi:10.1172/jci.insight.89620 · Cited by 88
Mitochondrial Sirtuins in cardiometabolic diseases
Tang, X., Chen, X., Chen, H., & Liu, D. (2017) · Clinical Science · doi:10.1042/cs20160685 · Cited by 87
Satoh, T., Wang, L., Espinosa‐Díez, C., Wang, B., Hahn, S. A., Noda, K., Rochon, E. R., Dent, M. R., Levine, A. R., Baust, J., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.053889 · Cited by 87
Mechanisms underlying blood pressure reduction by dietary inorganic nitrate
Carlström, M., Lundberg, J. O., & Weitzberg, E. (2018) · Acta Physiologica · doi:10.1111/apha.13080 · Cited by 87
Animal models of pulmonary hypertension: Getting to the heart of the problem
Dignam, J. P., Scott, T., Kemp‐Harper, B. K., & Hobbs, A. J. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15444 · Cited by 90
Meng, Q., Lai, Y., Kelly, N. J., Bueno, M., Baust, J., Bachman, T. N., Goncharov, D. A., Vanderpool, R. R., Radder, J. E., HU, J. L., et al. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0177oc · Cited by 81
Frataxin deficiency promotes endothelial senescence in pulmonary hypertension
Culley, M. K., Zhao, J., Tai, Y., Tang, Y., Perk, D., Negi, V., Yu, Q., Woodcock, C.-. C., Handen, A. L., Speyer, G., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci136459 · Cited by 81
Gheibi, S., Bakhtiarzadeh, F., Jeddi, S., Farrokhfall, K., Zardooz, H., & Ghasemi, A. (2017) · Nitric Oxide · doi:10.1016/j.niox.2017.01.003 · Cited by 79
Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation
Vaibhav, K., Braun, M., Khan, M. B., Fatima, S., Saad, N., Shankar, A., Khan, Z. T., Harris, R. B. S., Yang, Q., Huo, Y., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171905 · Cited by 79
Luteolin Protects Against CIRI, Potentially via Regulation of the SIRT3/AMPK/mTOR Signaling Pathway
Liu, S., Su, Y., Sun, B., Hao, R., Pan, S., Gao, X., Dong, X., Ismail, A. M., & Han, B. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03108-w · Cited by 79
Hezel, M. P., Peleli, M., Liu, M. R., Zollbrecht, C., Jensen, B. L., Checa, A., Giulietti, A., Wheelock, C. E., Lundberg, J. O., Weitzberg, E., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.07.025 · Cited by 73
Examining the clinical relevance of metformin as an antioxidant intervention
Buczyńska, A., Sidorkiewicz, I., Kretowski, A. J., & Adamska, A. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1330797 · Cited by 77
Endothelial Senescence: A New Age in Pulmonary Hypertension
Culley, M. K., & Chan, S. Y. (2022) · Circulation Research · doi:10.1161/circresaha.121.319815 · Cited by 71
Extranuclear Sirtuins and Metabolic Stress
Elkhwanky, M., & Hakkola, J. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7270 · Cited by 67
The Role of SIRT3 in the Brain Under Physiological and Pathological Conditions
Sidorova‐Darmos, E., Sommer, R., & Eubanks, J. H. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00196 · Cited by 66
Endothelial nitric oxide synthase-derived nitric oxide in the regulation of metabolism
Τενοπούλου, Μ., & Doulias, P. (2020) · F1000Research · doi:10.12688/f1000research.19998.1 · Cited by 67
Roles of Sirtuins in Cardiovascular Diseases: Mechanisms and Therapeutics
Ding, Y.-N., Wang, H.-Y., Chen, X.-F., Tang, X., & Chen, H. (2025) · Circulation Research · doi:10.1161/circresaha.124.325440 · Cited by 67
Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease
Huston, J., & Shah, S. J. (2022) · Circulation Research · doi:10.1161/circresaha.122.319967 · Cited by 61
Gao, S., Liu, X., Li, T., Chen, L., Feng, Y., Wang, Y., Yin, Y., Little, P. J., Wu, X., Xu, S., et al. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01152-0 · Cited by 65
Reddy, Y. N. V., Lewis, G. D., Shah, S. J., LeWinter, M. M., Semigran, M. J., Dávila‐Román, V. G., Anstrom, K. J., Hernandez, A. F., Braunwald, E., Redfield, M. M., et al. (2017) · Circulation Heart Failure · doi:10.1161/circheartfailure.117.003862 · Cited by 61
Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity
He, L., Liu, F., & Li, J. (2021) · Cardiovascular Toxicology · doi:10.1007/s12012-020-09626-x · Cited by 60
Gevaert, A. B., Lemmens, K., Vrints, C. J., & Craenenbroeck, E. M. V. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4865756 · Cited by 60
Xiao, Y., Chen, P., Zhou, R.-L., Zhang, Y., Tian, Z., & Zhang, S. (2020) · Aging and Disease · doi:10.14336/ad.2020.0111 · Cited by 59
From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease
Liu, H., Huang, Y., Huang, M., Wang, M., Ming, Y., Chen, W., Chen, Y., Tang, Z., & Jia, B. (2023) · European Journal of Medical Research · doi:10.1186/s40001-023-01413-y · Cited by 58
Sirtuin 3: Emerging therapeutic target for cardiovascular diseases
Cao, M., Zhao, Q., Sun, X., Qian, H., Lyu, S., Chen, R., Xia, H., & Yuan, W. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.01.005 · Cited by 59
Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension
Sun, W., & Chan, S. Y. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00204 · Cited by 57
Emerging Metabolic Therapies in Pulmonary Arterial Hypertension
Harvey, L. D., & Chan, S. Y. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6040043 · Cited by 59
Cardiovascular complications in patients with sickle cell disease
Gladwin, M. T. (2017) · Hematology · doi:10.1182/asheducation-2017.1.423 · Cited by 56
Right heart in pulmonary hypertension: from adaptation to failure
Ren, X., Johns, R. A., & Gao, W. D. (2019) · Pulmonary Circulation · doi:10.1177/2045894019845611 · Cited by 56
PPARγ is a gatekeeper for extracellular matrix and vascular cell homeostasis
Kökény, G., Calvier, L., Legchenko, E., Chouvarine, P., Mozes, M. M., & Hansmann, G. (2019) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000580 · Cited by 55
Myeloid Cell Derived IL1β Contributes to Pulmonary Hypertension in HFpEF
Agrawal, V., Kropski, J. A., Gokey, J. J., Kobeck, E., Murphy, M. B., Murray, K. T., Fortune, N. L., Moore, C. S., Meoli, D. F., Monahan, K., et al. (2023) · Circulation Research · doi:10.1161/circresaha.123.323119 · Cited by 52
SIRT3 in cardiovascular diseases: Emerging roles and therapeutic implications
Lü, Y., Wang, Y., Wang, X., Chen, H., Cai, Z., & Xiang, M. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.06.236 · Cited by 52
Molecular mechanisms of action of metformin: latest advances and therapeutic implications
Zhu, H., Jia, Z., Li, Y. R., & Danelisen, I. (2023) · Clinical and Experimental Medicine · doi:10.1007/s10238-023-01051-y · Cited by 59
Cardiovascular Protection by Metformin: Latest Advances in Basic and Clinical Research
Li, J. Z., & Li, Y. R. (2023) · Cardiology · doi:10.1159/000531432 · Cited by 57
wang, J., Ping, H., Pan, X., Xia, C., Zhang, H., Xiong, Y., Yuan, Z. K., Yuan, Z., Liu, J., Meng, C., et al. (2022) · Phytotherapy Research · doi:10.1002/ptr.7608 · Cited by 49
Sickle cell disease: at the crossroads of pulmonary hypertension and diastolic heart failure
Wood, K. C., Gladwin, M. T., & Straub, A. C. (2019) · Heart · doi:10.1136/heartjnl-2019-314810 · Cited by 48
Yang, Y., Tang, X., Yao, T. S., Zhang, Y., Zhong, Y., Wu, S., Wang, Y., & Pan, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-51990-z · Cited by 47
Signaling pathways and targeted therapy for pulmonary hypertension
Adu‐Amankwaah, J., Shi, Y., Song, H., Ma, Y., Liu, J., Wang, H., Yuan, J., Sun, K., Hu, Q., & Tan, R. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02287-8 · Cited by 52
Schiffer, T. A., Lundberg, J. O., Weitzberg, E., & Carlström, M. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165811 · Cited by 49
Agrawal, V., Lahm, T., Hansmann, G., & Hemnes, A. R. (2020) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-20-404 · Cited by 50
Keyhanmanesh, ., Hamidian, G., Alipour, M. R., Ranjbar, M., & Oghbaei, H. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.09.019 · Cited by 46
Whitaker, M., Nair, V., Sinari, S. A., Dherange, P., Natarajan, B., Trutter, L., Brittain, E. L., Hemnes, A. R., Austin, E. D., Patel, K. R., et al. (2018) · The American Journal of Medicine · doi:10.1016/j.amjmed.2017.12.046 · Cited by 44
Zollbrecht, C., Persson, A. E. G., Lundberg, J. O., Weitzberg, E., & Carlström, M. (2016) · Redox Biology · doi:10.1016/j.redox.2016.09.015 · Cited by 41
Right ventricular dysfunction and remodeling in diabetic cardiomyopathy
Kang, Y., Wang, S., Huang, J., Cai, L., & Keller, B. B. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00440.2018 · Cited by 40
Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases
Silaghi, C. N., Farcas, M. F., & Craciun, A. M. (2021) · Biomedicines · doi:10.3390/biomedicines9111574 · Cited by 37
The Effects of Metformin on Obesity-Induced Dysfunctional Retinas
Kim, A. J., Chang, J. Y.-A., Shi, L., Chang, R. C.-A., Ko, M. L., & Ko, G. Y.-P. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20691 · Cited by 38
Diabetes and Excess Aldosterone Promote Heart Failure With Preserved Ejection Fraction
Hegyi, B., Hernández, J. M., Ko, C. Y., Hong, J., Shen, E. Y., Spencer, E. R., Smoliarchuk, D., Navedo, M. F., Bers, D. M., & Bossuyt, J. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.027164 · Cited by 39
The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction
Dolinsky, V. W. (2017) · Biological Chemistry · doi:10.1515/hsz-2016-0316 · Cited by 37
Brittain, E. L., Thenappan, T., Huston, J., Agrawal, V., Lai, Y., Dixon, D., Ryan, J. J., Lewis, E. F., Redfield, M. M., Shah, S. J., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001079 · Cited by 36
Wang, L., Halliday, G., Huot, J. R., Satoh, T., Baust, J., Fisher, A. J., Cook, T. G., HU, J. L., Avolio, T., Goncharov, D. A., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313883 · Cited by 37
Lambert, M., Mendes‐Ferreira, P., Ghigna, M., Ribeuz, H. L., Adão, R., Boët, A., Capuano, V., Rücker‐Martin, C., Brás‐Silva, C., Quarck, R. A., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab016 · Cited by 36
Pulmonary Hypertension in Left Heart Disease
Reddy, Y. N. V., & Borlaug, B. A. (2021) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2020.11.002 · Cited by 36
AMPK and Pulmonary Hypertension: Crossroads Between Vasoconstriction and Vascular Remodeling
Zhao, Q., Song, P., & Zou, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.691585 · Cited by 37
SIRT6 in Vascular Diseases, from Bench to Bedside
Ren, S., Chen, X., Gong, H., Wang, H., Wu, C. F., Li, P., Chen, X., Qu, J.-H., & Tang, X. (2022) · Aging and Disease · doi:10.14336/ad.2021.1204 · Cited by 35
The yin and yang faces of the mitochondrial deacetylase sirtuin 3 in age-related disorders
Gomes, P., Viana, S., Nunes, S., Rolo, A. P., Palmeira, C. M., & Reis, F. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100983 · Cited by 34
Reddy, Y. N. V., Stewart, G. M., Obokata, M., Koepp, K. E., & Borlaug, B. A. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2093 · Cited by 33
Goncharov, D. A., Goncharova, E. A., Tofovic, S. P., HU, J. L., Baust, J., Pena, A. Z., Ray, A., Rode, A., Vanderpool, R. R., Mora, A. L., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201801-0022le · Cited by 34
Sun, L., Leng, R., Liu, M., Su, M., He, Q., Zhang, Z., Liu, Z., Wang, Z., Jiang, H., Wang, L., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci181928 · Cited by 38
Metadata
- 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
- Venue
- Circulation
- Published
- 2016-02-23
- Volume
- 133
- Issue
- 8
- Pages
- 717-731
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- 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
