ArticleCardiovascular diabetology2010
Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol.
Article in Cardiovascular diabetology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- One-carbon metabolism and risk of PCOS: insights from Mendelian randomization.Journal of ovarian research · 2025Article
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes.Nutrients · 2024Article
- Associations Between Serum Folate Level and HOMA-IR in Chinese Patients with Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Genome Editing and Diabetic Cardiomyopathy.Advances in experimental medicine and biology · 2023Article
- Exercise Augments the Effect of SGLT2 Inhibitor Dapagliflozin on Experimentally Induced Diabetic Cardiomyopathy, Possible Underlying Mechanisms.Metabolites · 2022Article
- Long-Acting Thioredoxin Ameliorates Doxorubicin-Induced Cardiomyopathy via Its Anti-Oxidative and Anti-Inflammatory Action.Pharmaceutics · 2022Article
- Sustained Inhibition of NF-κB Activity Mitigates Retinal Vasculopathy in Diabetes.The American journal of pathology · 2021Article
- Involvements of Hyperhomocysteinemia in Neurological Disorders.Metabolites · 2021Review
- Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression.Frontiers in immunology · 2021Article
- Association between gene promoter methylation of the one-carbon metabolism pathway and serum folate among patients with hyperhomocysteinemia.European journal of clinical nutrition · 2020Article
- Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress conditionCanadian journal of physiology and pharmacology · 2019Review
- Hydrogen Sulfide Ameliorates Homocysteine-Induced Cardiac Remodeling and Dysfunction.Frontiers in physiology · 2019Article
- Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of cystathionine-β-synthase mutant mice via PPAR-γ/VEGF axis.Physiological reports · 2018Article
- MiR-133a Mimic Alleviates T1DM-Induced Systolic Dysfunction in Akita: An MRI-Based Study.Frontiers in physiology · 2018Article
- Targeting miRNA for Therapy of Juvenile and Adult Diabetic Cardiomyopathy.Advances in experimental medicine and biology · 2018Article
- Homocysteine as a Pathological Biomarker for Bone Disease.Journal of cellular physiology · 2017Review
- Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.Journal of cellular biochemistry · 2017Review
- Novel Anti-fibrotic Therapies.Frontiers in pharmacology · 2017Review
- Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing.PloS one · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear.
methodsDiabetic Akita (Ins2+/-) and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/-) were used for M-mode echocardiography at the age of four and twenty four weeks. The cardiac rings from WT, Akita and hybrid (Ins2+/-/CBS+/-) of Akita and CBS+/- were treated with different doses of acetylcholine (an endothelial dependent vasodilator). High performance liquid chromatography (HPLC) was performed for determining plasma homocysteine (Hcy) level in the above groups. Akita was treated with ciglitazone (CZ) - a PPAR gamma agonist and tempol-an anti-oxidant, separately and their effects on cardiac remodeling were assessed.
resultsAt twenty four week, Akita mice were hyperglycemic and HHcy. They have increased end diastolic diameter (EDD). In their heart PPAR gamma, tissue inhibitor of metalloproteinase-4 (TIMP-4) and anti-oxidant thioredoxin were attenuated whereas matrix metalloproteinase (MMP)-9, TIMP-3 and NADPH oxidase 4 (NOX4) were induced. Interestingly, they showed synergism between HHcy and hyperglycemia for endothelial-myocyte (E-M) uncoupling. Additionally, treatment with CZ alleviated MMP-9 activity and fibrosis, and improved EDD. On the other hand, treatment with tempol reversed cardiac remodeling in part by restoring the expressions of TIMP-3,-4, thioredoxin and MMP-9.
conclusionsEndogenous homocysteine exacerbates diabetic cardiomyopathy by attenuating PPAR gamma and inducing E-M uncoupling leading to diastolic dysfunction. PPAR gamma agonist and tempol mitigates oxidative stress and ameliorates diastolic dysfunction in diabetes.
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Registered trials
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