ArticleCirculation2009
Protein tyrosine phosphatase 1B, a major regulator of leptin-mediated control of cardiovascular function.
Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Leptin and Associated Neural Pathways Underlying Obesity-Induced Hypertension.Comprehensive Physiology · 2025Review
- Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside.Journal of clinical medicine · 2024Review
- NADPH oxidase 1 promotes hepatic steatosis in obese mice and is abrogated by augmented skeletal muscle mass.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Type 1 Diabetes Impairs Endothelium-Dependent Relaxation Via Increasing Endothelial Cell Glycolysis Through Advanced Glycation End Products, PFKFB3, and Nox1-Mediated Mechanisms.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Article
- Adipokines: Deciphering the cardiovascular signature of adipose tissue.Biochemical pharmacology · 2022Review
- Small extracellular vesicles from Ptpn1-deficient macrophages alleviate intestinal inflammation by reprogramming macrophage polarization via lactadherin enrichment.Redox biology · 2022Article
- Endothelial leptin receptor is dispensable for leptin-induced sympatho-activation and hypertension in male mice.Vascular pharmacology · 2022Article
- Friend or foe? Unraveling the complex roles of protein tyrosine phosphatases in cardiac disease and development.Cellular signalling · 2022Review
- Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy.International journal of molecular sciences · 2021Article
- Leptin Receptor Blockade Attenuates Hypertension, but Does Not Affect Ventilatory Response to Hypoxia in a Model of Polygenic Obesity.Frontiers in physiology · 2021Article
- HIV Protease Inhibitor Ritonavir Impairs Endothelial Function Via Reduction in Adipose Mass and Endothelial Leptin Receptor-Dependent Increases in NADPH Oxidase 1 (Nox1), C-C Chemokine Receptor Type 5 (CCR5), and Inflammation.Journal of the American Heart Association · 2020Article
- Selective deficiency in endothelial PTP1B protects from diabetes and endoplasmic reticulum stress-associated endothelial dysfunction via preventing endothelial cell apoptosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Article
- Combined network pharmacology and virtual reverse pharmacology approaches for identification of potential targets to treat vascular dementia.Scientific reports · 2020Article
- Leptin Restores Endothelial Function via Endothelial PPARγ-Nox1-Mediated Mechanisms in a Mouse Model of Congenital Generalized Lipodystrophy.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Obesity, kidney dysfunction and hypertension: mechanistic links.Nature reviews. Nephrology · 2019Review
- Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function.F1000Research · 2019Review
- New roles of aldosterone and mineralocorticoid receptors in cardiovascular disease: translational and sex-specific effects.American journal of physiology. Heart and circulatory physiology · 2018Article
- Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in regulation of liver lipids and glucose tolerance.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Protein tyrosine phosphatases in cardiac physiology and pathophysiology.Heart failure reviews · 2018Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundObesity causes hypertension and sympathoactivation, a process proposed to be mediated by leptin. Protein tyrosine phosphatase 1B (PTP1B), a major new pharmaceutical target in the treatment of obesity and type II diabetes mellitus, constrains the metabolic actions of leptin, but the extent to which PTP1B regulates its cardiovascular effects is unclear. This study examined the hypothesis that PTP1B is a negative regulator of the cardiovascular effects of leptin. METHODS AND
resultsPTP1B knockout mice had lower body fat but higher mean arterial pressure (116+/-5 versus 105+/-5 mm Hg, P<0.05) than controls. Leptin infusion produced a greater anorexic effect in PTP1B knockout mice and a marked increase in mean arterial pressure (135+/-5 mm Hg) in PTP1B knockout mice only. The decrease in mean arterial pressure in response to ganglionic blockade was higher in PTP1B knockout mice (-38+/-3% versus -29+/-3%, P<0.05), which suggests increased sympathetic tone. PTP1B deletion blunted mean arterial pressure responses to phenylephrine injection (55+/-10% versus 93+/-7%, P<0.05). Phenylephrine-induced aortic contraction was reduced in PTP1B knockout mice (57.7+/-9% versus 96.3+/-12% of KCl, P<0.05), consistent with desensitization to chronically elevated sympathetic tone. Furthermore, PTP1B deletion significantly reduced gene expression of 3 alpha(1)-adrenergic receptor subtypes, consistent with blunted constriction to phenylephrine.
conclusionsThese data indicate that PTP1B is a key regulator of the cardiovascular effects of leptin and that reduced vascular adrenergic reactivity provides a compensatory limit to the effects of leptin on mean arterial pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.