ArticleBiochemical and biophysical research communications2016
Primacy of cardiac chymase over angiotensin converting enzyme as an angiotensin-(1-12) metabolizing enzyme.
Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.Bioscience reports · 2024Review
- Is It Still Relevant to Discover New ACE Inhibitors from Natural Products? YES, but Only with Comprehensive Approaches to Address the Patients' Real Problems: Chronic Dry Cough and Angioedema.Molecules (Basel, Switzerland) · 2023Review
- Internalization of Angiotensin-(1-12) in Adult Retinal Pigment Epithelial-19 Cells.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Plasma Chymase Activity Reflects the Change in Hemodynamics Observed after the Surgical Treatment of Patent Ductus Arteriosus in Dogs.Veterinary sciences · 2022Article
- Does the Naked Emperor Parable Apply to Current Perceptions of the Contribution of Renin Angiotensin System Inhibition in Hypertension?Current hypertension reports · 2022Review
- Immunoneutralization of human angiotensin-(1-12) with a monoclonal antibody in a humanized model of hypertension.Peptides · 2022Article
- The Angiotensin-(1-12)/Chymase axis as an alternate component of the tissue renin angiotensin system.Molecular and cellular endocrinology · 2021Review
- Angiotensin (1-12) in Humans With Normal Blood Pressure and Primary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats.Frontiers in pharmacology · 2021Article
- The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential.Cellular signalling · 2020Review
- Extended Cleavage Specificity of the Rat Vascular Chymase, a Potential Blood Pressure Regulating Enzyme Expressed by Rat Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Article
- Twenty years of progress in angiotensin converting enzyme 2 and its link to SARS-CoV-2 disease.Clinical science (London, England : 1979) · 2020Review
- Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle?EMBO molecular medicine · 2020Review
- Is Sex a Determinant of COVID-19 Infection? Truth or Myth?Current hypertension reports · 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
- Association between chymase gene polymorphisms and atrial fibrillation in Chinese Han population.BMC cardiovascular disorders · 2019Article
- Angiotensin-(1-12)/chymase axis modulates cardiomyocyte L-type calcium currents in rats expressing human angiotensinogen.International journal of cardiology · 2019Article
- Mast cell peptidases (carboxypeptidase A and chymase)-mediated hydrolysis of human angiotensin-(1-12) substrate.Biochemical and biophysical research communications · 2019Article
- Estrogen modulates the differential expression of cardiac myocyte chymase isoforms and diastolic function.Molecular and cellular biochemistry · 2019Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
We showed previously that rat angiotensin-(1-12) [Ang-(1-12)] is metabolized by chymase and angiotensin converting enzyme (ACE) to generate Angiotensin II (Ang II). Here, we investigated the affinity of cardiac chymase and ACE enzymes for Ang-(1-12) and Angiotensin I (Ang I) substrates. Native plasma membranes (PMs) isolated from heart and lung tissues of adult spontaneously hypertensive rats (SHR) were incubated with radiolabeled (125)I-Ang-(1-12) or (125)I-Ang I, in the absence or presence of a chymase or ACE inhibitor (chymostatin and lisinopril, respectively). Products were quantitated by HPLC connected to an in-line flow-through gamma detector. The rate of (125)I-Ang II formation from (125)I-Ang-(1-12) by chymase was significantly higher (heart: 7.0 ± 0.6 fmol/min/mg; lung: 33 ± 1.2 fmol/min/mg, P < 0.001) when compared to (125)I-Ang I substrate (heart: 0.8 ± 0.1 fmol/min/mg; lung: 2.1 ± 0.1 fmol/min/mg). Substrate affinity of (125)I-Ang-(1-12) for rat cardiac chymase was also confirmed using excess unlabeled Ang-(1-12) or Ang I (0-250 μM). The rate of (125)I-Ang II formation was significantly lower using unlabeled Ang-(1-12) compared to unlabeled Ang I substrate. Kinetic data showed that rat chymase has a lower Km (64 ± 6.3 μM vs 142 ± 17 μM), higher Vmax (13.2 ± 1.3 μM/min/mg vs 1.9 ± 0.2 μM/min/mg) and more than 15-fold higher catalytic efficiency (ratio of Vmax/Km) for Ang-(1-12) compared to Ang I substrate, respectively. We also investigated ACE mediated hydrolysis of (125)I-Ang-(1-12) and (125)I-Ang I in solubilized membrane fractions of the SHR heart and lung. Interestingly, no significant difference in (125)I-Ang II formation by ACE was detected using either substrate, (125)I-Ang-(1-12) or (125)I-Ang I, both in the heart (1.8 ± 0.2 fmol/min/mg and 1.8 ± 0.3 fmol/min/mg, respectively) and in the lungs (239 ± 25 fmol/min/mg and 248 ± 34 fmol/min/mg, respectively). Compared to chymase, ACE-mediated Ang-(1-12) metabolism in the heart was several fold lower. Overall our findings suggest that Ang-(1-12), not Ang I, is the better substrate for Ang II formation by chymase in adult rats. In addition, this confirms our previous observation that chymase (rather than ACE) is the main hydrolyzing enzyme responsible for Ang II generation from Ang-(1-12) in the adult rat heart.
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