ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Cardiac angiotensin-(1-12) expression and systemic hypertension in rats expressing the human angiotensinogen gene.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Angiotensin Receptor Blocker is Associated with a Lower Fracture Risk: An Updated Systematic Review and Meta-Analysis.International journal of clinical practice · 2022Pooled it
- Article
- The renin-angiotensin system biomolecular cascade: a 2022 update of newer insights and concepts.Kidney international supplements · 2022Review
- Immunoneutralization of human angiotensin-(1-12) with a monoclonal antibody in a humanized model of hypertension.Peptides · 2022Article
- Risk factors for the delayed viral clearance in COVID-19 patients.Journal of clinical hypertension (Greenwich, Conn.) · 2021Article
- 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
- Noncanonical Mechanisms for Direct Bone Marrow Generating Ang II (Angiotensin II) Predominate in CD68 Positive Myeloid Lineage Cells.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Angiotensin-(1-12)/chymase axis modulates cardiomyocyte L-type calcium currents in rats expressing human angiotensinogen.International journal of cardiology · 2019Article
- An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology.Journal of cardiovascular development and disease · 2019 · on this mapReview
- Activation of the Human Angiotensin-(1-12)-Chymase Pathway in Rats With Human Angiotensinogen Gene Transcripts.Frontiers in cardiovascular medicine · 2019Article
- Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease.Pharmacological research · 2017Review
- Analysis of the function of microRNA-375 in humans using bioinformatics.Biomedical reports · 2017Article
- Role of Tissue Renin-angiotensin System and the Chymase/angiotensin-( 1-12) Axis in the Pathogenesis of Diabetic Retinopathy.Current medicinal chemistry · 2017Review
- Primacy of cardiac chymase over angiotensin converting enzyme as an angiotensin-(1-12) metabolizing enzyme.Biochemical and biophysical research communications · 2016Article
- Intracrine angiotensin II functions originate from noncanonical pathways in the human heart.American journal of physiology. Heart and circulatory physiology · 2016Review
- Is chymase 1 a therapeutic target in cardiovascular disease?Expert opinion on therapeutic targetsReview
- COVID-19 and hypertension.Journal of the renin-angiotensin-aldosterone system : JRAASArticle
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Angiotensin-(1-12) [ANG-(1-12)] is processed into ANG II by chymase in rodent and human heart tissue. Differences in the amino acid sequence of rat and human ANG-(1-12) render the human angiotensinogen (hAGT) protein refractory to cleavage by renin. We used transgenic rats harboring the hAGT gene [TGR(hAGT)L1623] to assess the non-renin-dependent effects of increased hAGT expression on heart function and arterial pressure. Compared with Sprague-Dawley (SD) control rats (n= 11), male homozygous TGR(hAGT)L1623 (n= 9) demonstrated sustained daytime and nighttime hypertension associated with no changes in heart rate but increased heart rate lability. Increased heart weight/tibial length ratio and echocardiographic indexes of cardiac hypertrophy were associated with modest reduction of systolic function in hAGT rats. Robust human ANG-(1-12) immunofluorescence within myocytes of TGR(hAGT)L1623 rats was associated with a fourfold increase in cardiac ANG II content. Chymase enzymatic activity, using the rat or human ANG-(1-12) as a substrate, was not different in the cardiac tissue of SD and hAGT rats. Since both cardiac angiotensin-converting enzyme (ACE) and ACE2 activities were not different among the two strains, the changes in cardiac structure and function, blood pressure, and left ventricular ANG II content might be a product of an increased cardiac expression of ANG II generated through a non-renin-dependent mechanism. The data also underscore the existence in the rat of alternate enzymes capable of acting on hAGT protein. Homozygous transgenic rats expressing the hAGT gene represent a novel tool to investigate the contribution of human relevant renin-independent cardiac ANG II formation and function.
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