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 37 papers, 2 of them syntheses that pooled it.
What it found
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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
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Circulating Amyloid and Misfolded Biomarkers in Early Myocardial Injury: A Systematic Review and Epistemic Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- The causative role of amyloidosis in the cardiac complications of Alzheimer's disease: a comprehensive systematic review.The Journal of physiology · 2026Pooled it
- Associations of plasma metabolites with protein biomarkers linked to Alzheimer's disease pathology in the Rotterdam Study.Alzheimer's research & therapy · 2026Article
- Effects of HA1, a probucol analogue, and APOC3 siRNA on lipoprotein and amyloid-β metabolism and neurovascular dysfunction in type 2 diabetic mice.Frontiers in pharmacology · 2026Article
- 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
- Cerebrovascular protective functions of amyloid precursor protein: Progress and therapeutic prospects.Pharmacology & therapeutics · 2025Review
- 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
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.
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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.