ArticleThe Journal of clinical investigation2010
Mast cell chymase limits the cardiac efficacy of Ang I-converting enzyme inhibitor therapy in rodents.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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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
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- Clinical efficacy and safety of nuanxin capsule for chronic heart failure: A systematic review and meta-analysis.Medicine · 2018Pooled it
- Trial
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- Assessing Venous Congestion in Heart Failure: A Review of Splanchnic, Cardiac, and Pulmonary Ultrasound: Part 2: Contrast-Enhanced Ultrasound and Shear Wave.Journal of clinical medicine · 2026Review
- Endocrine regulation of cardiac fibrosis: implications for HFpEF.Frontiers in endocrinology · 2026Review
- Molecular insights into the inhibition of angiotensin-converting enzyme 1 by hemopressin peptides.Scientific reports · 2024Article
- Aprotinin (I): Understanding the Role of Host Proteases in COVID-19 and the Importance of Pharmacologically Regulating Their Function.International journal of molecular sciences · 2024Review
- Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities.Circulation research · 2024Review
- Mast cells: a novel therapeutic avenue for cardiovascular diseases?Cardiovascular research · 2024Review
- Mast Cells in Cardiac Remodeling: Focus on the Right Ventricle.Journal of cardiovascular development and disease · 2024Review
- Kinin BPharmaceuticals (Basel, Switzerland) · 2023Article
- Feasibility study of intraoperative pericardial fluid biomarkers and length of stay after cardiac surgery.JTCVS techniques · 2023Article
- Impact of early pericardial fluid chymase activation after cardiac surgery.Frontiers in cardiovascular medicine · 2023Article
- Does the Naked Emperor Parable Apply to Current Perceptions of the Contribution of Renin Angiotensin System Inhibition in Hypertension?Current hypertension reports · 2022Review
- Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.Signal transduction and targeted therapy · 2022Article
- Remuscularization with triiodothyronine and βScientific reports · 2022Article
- Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19.Reviews in endocrine & metabolic disorders · 2022Review
- Article
- Kinins and chymase: the forgotten components of the renin-angiotensin system and their implications in COVID-19 disease.American journal of physiology. Lung cellular and molecular physiology · 2021Review
- Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review.The review of diabetic studies : RDS · 2021Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Ang I-converting enzyme (ACE) inhibitors are widely believed to suppress the deleterious cardiac effects of Ang II by inhibiting locally generated Ang II. However, the recent demonstration that chymase, an Ang II-forming enzyme stored in mast cell granules, is present in the heart has added uncertainty to this view. As discussed here, using microdialysis probes tethered to the heart of conscious mice, we have shown that chronic ACE inhibitor treatment did not suppress Ang II levels in the LV interstitial fluid (ISF) despite marked inhibition of ACE. However, chronic ACE inhibition caused a marked bradykinin/B2 receptor-mediated increase in LV ISF chymase activity that was not observed in mast cell-deficient KitW/KitW-v mice. In chronic ACE inhibitor-treated mast cell-sufficient littermates, chymase inhibition decreased LV ISF Ang II levels substantially, indicating the importance of mast cell chymase in regulating cardiac Ang II levels. Chymase-dependent processing of other regulatory peptides also promotes inflammation and tissue remodeling. We found that combined chymase and ACE inhibition, relative to ACE inhibition alone, improved LV function, decreased adverse cardiac remodeling, and improved survival after myocardial infarction in hamsters. These results suggest that chymase inhibitors could be a useful addition to ACE inhibitor therapy in the treatment of heart failure.
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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.