ArticleCardiovascular research2021
Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Heparanase gene deficiency suppresses atherosclerosis progression and enhances plaque stability in apolipoprotein E gene knockout mice with diabetes.Clinical science (London, England : 1979) · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Ferroptosis regulator NOX1 acts a diagnostic biomarker and mediates disease progression with the transcriptional regulation of STAT3 in glaucoma.Indian journal of ophthalmology · 2026Article
- Suppressive effect of chrysin on macrophage LC3B autophagy through miR-204-5p in diabetic atherosclerosis.Scientific reports · 2026Article
- Targeting endoplasmic reticulum stress and YAP/TAZ-SMAD1/5 signaling to ameliorate endothelial dysfunction in diabetes.Acta pharmacologica Sinica · 2026Article
- Apolipoprotein E ɛ3/ɛ4 genotype is associated with premature myocardial infarction: a hospital based retrospective study.BMC cardiovascular disorders · 2026Article
- Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications.Biological research · 2026Review
- Prodrug Strategies in Atherosclerosis: Targeted Delivery and Therapeutic Advances.Cardiovascular therapeutics · 2026Review
- Endothelin as a Treatment Target in Cardiovascular Diseases: A Recent Step Forward.Reviews in cardiovascular medicine · 2025Review
- Aqueous extract of Peristrophe bivalvis leaf alleviates oxidative stress in L-NAME-induced hypertensive rats.BMC complementary medicine and therapies · 2025Article
- Endothelin antagonists for hypertension: has their time finally arrived?Clinical science (London, England : 1979) · 2025Review
- The Role of Endothelin-1, Kidney Function and Diabetes in Patients With Coronary Artery Disease Underwent Percutaneous Coronary Intervention.Journal of diabetes · 2025Article
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Correlation Between Prognostic Nutritional Index and Heart Failure in Adults with Diabetes in the United States: Study Results from NHANES (1999-2016).Reviews in cardiovascular medicine · 2025Article
- The positive implication of natural antioxidants on oxidative stress-mediated diabetes mellitus complications.Journal, genetic engineering & biotechnology · 2024Review
- JNK Pathway-Associated Phosphatase Deficiency Facilitates Atherosclerotic Progression by Inducing T-Helper 1 and 17 Polarization and Inflammation in an ERK- and NF-κB Pathway-Dependent Manner.Journal of atherosclerosis and thrombosis · 2024Article
- Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.Molecules (Basel, Switzerland) · 2024Review
- Universal cell membrane camouflaged nano-prodrugs with right-side-out orientation adapting for positive pathological vascular remodeling in atherosclerosis.Chemical science · 2024Article
- Endothelin System in Hypertension and Chronic Kidney Disease.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism.Journal of cardiovascular translational research · 2024Review
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
aimsNADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe-/-) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. METHODS AND
resultsSix-week-old male Apoe-/- and eET-1/Apoe-/- mice with or without Nox1 (Nox1-/y) or Nox4 knockout (Nox4-/-) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe-/- mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe-/- and eET-1/Apoe-/-/Nox4-/- mice but not eET-1/Apoe-/-/Nox1y/- mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe-/- mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe-/- mice.
conclusionEndothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.
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