Trial reportCardiovascular diabetology2022
Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts.
Trial report in Cardiovascular diabetology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03546062 (Lipid Accumulation in Heart Transplant From Non-diabetic Donors to Diabetic Recipients), which is not on this map. Cited by 14 papers.
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.
Lipid Accumulation in Heart Transplant From Non-diabetic Donors to Diabetic Recipients
Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Hyperglycemia-Induced Endothelial Dysfunction: From Classical Pathogenetic Mechanisms to Emerging Insights into ACE2 Protective Action.International journal of molecular sciences · 2026Review
- Identification of non-cardiomyocytes marker genes in patients with diabetes and cardiomyopathy through single-cell analysis.PloS one · 2026Article
- Diabetic cardiomyopathy: a comprehensive review of diagnosis, management, and future directions.Diabetology & metabolic syndrome · 2025Review
- Expression of the Renin-Angiotensin System in the Heart, Aorta, and Perivascular Adipose Tissue in an Animal Model of Type 1 Diabetes.International journal of molecular sciences · 2025Article
- Serum Ang 1, Ang 1-7, and Mas levels as potential biomarkers in obstructive sleep apnea syndrome.Biomarkers in medicine · 2025Article
- "Emerging clinical approaches in diabetic cardiomyopathy: insights from clinical trials and future directions".Acta diabetologica · 2025Review
- Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin-Angiotensin System.Biomedicines · 2024Review
- Diabetes mellitus is associated to high-risk late gadolinium enhancement and worse outcomes in patients with nonischemic dilated cardiomyopathy.Cardiovascular diabetology · 2024Article
- Terminal trajectory of HbAFrontiers in endocrinology · 2024Article
- Esaxerenone Protects against Diabetic Cardiomyopathy via Inhibition of the Chemokine and PI3K-Akt Signaling Pathway.Biomedicines · 2023Article
- The RAAS Goodfellas in Cardiovascular System.Journal of clinical medicine · 2023Review
- Silicate Ions Derived from Calcium Silicate Extract Decelerate Ang II-Induced Cardiac Remodeling.Tissue engineering and regenerative medicine · 2023Article
- The emerging role of sacubitril/valsartan in pulmonary hypertension with heart failure.Frontiers in cardiovascular medicine · 2023Review
- Reviewing the Modern Therapeutical Options and the Outcomes of Sacubitril/Valsartan in Heart Failure.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control.
objectivesWe investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1-9, Ang 1-7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts.
methodsWe evaluated 197 first HTX recipients (107 non-T2DM, 90 T2DM). All patients were treated with angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) at hospital discharge. Patients underwent clinical evaluation (metabolic status, echocardiography, coronary CT-angiography, and endomyocardial biopsies). Biopsies were used to evaluate ACE2, GlycACE2, Ang 1-9, Ang 1-7, MasR, NAFT, and fibrosis.
resultsGlycACE2 was higher in T2DM compared tonon-T2DM cardiomyocytes. Moreover, reduced expressions of Ang 1-9, Ang 1-7, and MasR were observed, suggesting impaired effects of RAS-inhibition in diabetic hearts. Accordingly, biopsies from T2DM recipients showed higher fibrosis than those from non-T2DM recipients. Notably, the expression of GlycACE2 in heart biopsies was strongly dependent on glycemic control, as reflected by the correlation between mean plasma HbA1c, evaluated quarterly during the 12-month follow-up, and GlycACE2 expression.
conclusionPoor glycemic control, favoring GlycACE2, may attenuate the cardioprotective effects of RAS-inhibition. However, the achievement of tight glycemic control normalizes the anti-remodeling effects of RAS-inhibition.
trial registrationhttps://clinicaltrials.gov/ NCT03546062.
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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.