ArticleThe Journal of clinical investigation2020
Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The causative role of amyloidosis in the cardiac complications of Alzheimer's disease: a comprehensive systematic review.The Journal of physiology · 2026Pooled it
- Amyloid-beta (1-40) peptide is associated with systemic metabolic health.European journal of clinical investigation · 2026Article
- The Cognitive Changes Among Patients over 65 Years of Age in a Rural Area-The Preliminary Report of Protective and Predisposing Factors.Neurology international · 2025Article
- Interleukin 33 Promotes Liver Sinusoidal Endothelial Cell Dysfunction and Hepatic Fibrosis in Diabetic Mice.Diabetes & metabolism journal · 2025Article
- Metabolic Stress-Induced Choline Kinase α (CHKA) Activation in Endothelial Subpopulation Contributes to Diabetes-Associated Microvascular Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- How to measure and model cardiovascular aging.Cardiovascular research · 2025Review
- Intraoperative blood perfusion factors in free anterolateral thigh flap repair for diabetic foot ulcers: A retrospective analysis.World journal of diabetes · 2025Article
- BACE1 Inhibition Protects Against Type 2 Diabetes Mellitus by Restoring Insulin Receptor in Mice.International journal of molecular sciences · 2025Article
- The Peripheral Amyloid-β Nexus: Connecting Alzheimer's Disease with Atherosclerosis through Shared Pathophysiological Mechanisms.Neuromolecular medicine · 2025Review
- Network pharmacology combined with molecular docking and dynamics to assess the synergism of esculetin and phloretin against acute kidney injury-diabetes comorbidity.Molecular diversity · 2025Article
- Cerebrovascular Endothelial Dysfunction: Role of BACE1.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Experimental laboratory models as tools for understanding modifiable dementia risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: a comprehensive review.European journal of medical research · 2024Review
- Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity.Nature communications · 2024Article
- Serum amyloid beta 42 levels correlated with metabolic syndrome and its components.Frontiers in endocrinology · 2024Article
- Soluble and insoluble protein aggregates, endoplasmic reticulum stress, and vascular dysfunction in Alzheimer's disease and cardiovascular diseases.GeroScience · 2023Review
- Inactivation of BACE1 increases expression of endothelial nitric oxide synthase in cerebrovascular endothelium.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Blood-based Aβ42 increases in the earliest pre-pathological stage before decreasing with progressive amyloid pathology in preclinical models and human subjects: opening new avenues for prevention.Acta neuropathologica · 2022Article
- Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy.Journal of translational medicine · 2022Article
- BACE1: More than just a β-secretase.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
Corrections and comments
- Expression of concern
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Diabetes, obesity, and Alzheimer's disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein-cleaving (APP-cleaving) enzyme 1 (BACE1), APP, and β-amyloid (Aβ) are linked with vascular disease development and increased BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, increased Aβ, and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice increased plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction, and increased blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation, and raised blood pressure. In humans, increased plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP (cGMP), and protein kinase G (PKG) activity independently of diet, whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS/cGMP/PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.