ArticleAmerican journal of physiology. Heart and circulatory physiology2017
Chymase-dependent production of angiotensin II: an old enzyme in old hearts.
Article in American journal of physiology. Heart and circulatory physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Immunology of heart failure with preserved ejection fraction.Expert review of clinical immunology · 2025Pooled it
- Guidelines for authors and reviewers on antibody use in physiology studies.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- Angiotensin II and Cardiovascular Disease: Balancing Pathogenic and Protective Pathways.Current issues in molecular biology · 2025Review
- Renin-Angiotensin System: Updated Understanding and Role in Physiological and Pathophysiological States.Cureus · 2023Review
- Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis.International journal of molecular sciences · 2023Review
- Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Mechanisms of Cardiovascular System Injury Induced by COVID-19 in Elderly Patients With Cardiovascular History.Frontiers in cardiovascular medicine · 2022Review
- Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease.International journal of molecular sciences · 2021Article
- The Impact of the Renin-Angiotensin-Aldosterone System on Inflammation, Coagulation, and Atherothrombotic Complications, and to Aggravated COVID-19.Frontiers in pharmacology · 2021Review
- Aging- and gender-related modulation of RAAS: potential implications in COVID-19 disease.Vascular biology (Bristol, England) · 2021Review
- Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle?EMBO molecular medicine · 2020Review
- The contribution of chymase-dependent formation of ANG II to cardiac dysfunction in metabolic syndrome of young rats: roles of fructose and EETs.American journal of physiology. Heart and circulatory physiology · 2020Article
- Noncanonical Mechanisms for Direct Bone Marrow Generating Ang II (Angiotensin II) Predominate in CD68 Positive Myeloid Lineage Cells.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Covid-19 and the Renin Angiotensin System: Implications for the Older Adults.The journal of nutrition, health & aging · 2020Review
- Role of Renin-Angiotensin-System in Human Breast Cancer Cells: Is There a Difference in Regulation of Angiogenesis between Hormone-Receptor Positive and Negative Breast Cancer Cells?Geburtshilfe und Frauenheilkunde · 2019Article
- Histone deacetylase inhibition disturbs the balance between ACE and chymase expression in endothelial cells: a potential mechanism of chymase activation in preeclampsia.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly.Pharmacology & therapeutics · 2019Review
- Chymase inhibitors for the treatment of cardiac diseases: a patent review (2010-2018).Expert opinion on therapeutic patents · 2018Review
- Critical role of the chymase/angiotensin-(1-12) axis in modulating cardiomyocyte contractility.International journal of cardiology · 2018Article
- Statistical considerations in reporting cardiovascular research.American journal of physiology. Heart and circulatory physiology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Age-dependent alteration of the renin-angiotensin system (RAS) and generation of angiotensin II (Ang II) are well documented. By contrast, RAS-independent generation of Ang II in aging and its responses to exercise have not been explored. To this end, we examined the effects of chymase, a secretory serine protease, on the angiotensin-converting enzyme (ACE)-independent conversion of Ang I to Ang II. We hypothesized that age-dependent alteration of cardiac Ang II formation is chymase dependent in nature and is prevented by exercise training. Experiments were conducted on hearts isolated from young (3 mo), aged sedentary (24 mo), and aged rats chronically exercised on a treadmill. In the presence of low Ang I levels and downregulation of ACE expression/activity, cardiac Ang II levels were significantly higher in aged than young rats, suggesting an ACE-independent response. Aged hearts also displayed significantly increased chymase expression and activity, as well as upregulation of tryptase, a biological marker of mast cells, confirming a mast cell-sourced increase in chymase. Coincidently, cardiac superoxide produced from NADPH oxidase (Nox) was significantly enhanced in aged rats and was normalized by exercise. Conversely, a significant reduction in cardiac expression of ACE2 followed by lower Ang 1-7 levels and downregulation of the Mas receptor (binding protein of Ang 1-7) in aged rats were completely reversed by exercise. In conclusion, local formation of Ang II is increased in aged hearts, and chymase is primarily responsible for this increase. Chronic exercise is able to normalize the age-dependent alterations via compromising chymase/Ang II/angiotensin type 1 receptor/Nox actions while promoting ACE2/Ang 1-7/MasR signaling. NEW & NOTEWORTHY: Aging increases angiotensin-converting enzyme (ACE)-independent production of cardiac angiotensin II (Ang II), a response that is driven by chymase in an exercise-reversible manner. These findings highlight chymase, in addition to ACE, as an important therapeutic target in the treatment and prevention of Ang II-induced deterioration of cardiac function in the elderly.
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Registered trials
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