Sayaka Nagata1, Jasmina Varagic2, Neal D Kon3, Hao Wang4, Leanne Groban4, Stephen W Simington1, Sarfaraz Ahmad1, Louis J Dell'Italia5, Jessica L VonCannon1, Dwight Deal3, Carlos M Ferrario6. 1. Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA. 2. Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA. 3. Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA. 4. Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA. 5. Birmingham Veterans Affair Medical Center, University of Alabama Medical Center, Birmingham, AL, USA Division of Cardiovascular Disease, Department of Medicine, University of Alabama Medical Center, Birmingham, AL, USA. 6. Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA cferrari@wakehealth.edu.
Abstract
OBJECTIVE: Heart chymase rather than angiotensin converting enzyme has higher specificity for angiotensin (Ang) I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. We address here whether Ang-(1-12) and chymase gene expression and activity are detected in the atrial appendages of 44 patients (10 females) undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. METHODS AND RESULTS: Immunoreactive Ang-(1-12) expression was 54% higher in left atrial compared with right atrial appendages. This was associated with higher abundance of left atrial appendage chymase gene transcripts and chymase activity, but no differences in angiotensinogen mRNA. Atrial chymase enzymatic activity was highly correlated with left atrial but not right atrial enlargement as determined by echocardiography, while both tyrosine hydroxylase and neuropeptide Y atrial appendage mRNAs correlated with atrial angiotensinogen mRNAs. CONCLUSIONS: Higher Ang-(1-12) expression and upregulation of chymase gene transcripts and enzymatic activity from the atrial appendages connected to the enlarged left versus right atrial chambers of subjects with left heart disease defines a role of this alternate Ang II forming pathway in the processes accompanying adverse atrial and ventricular remodeling.
OBJECTIVE: Heart chymase rather than angiotensin converting enzyme has higher specificity for angiotensin (Ang) I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. We address here whether Ang-(1-12) and chymase gene expression and activity are detected in the atrial appendages of 44 patients (10 females) undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. METHODS AND RESULTS: Immunoreactive Ang-(1-12) expression was 54% higher in left atrial compared with right atrial appendages. This was associated with higher abundance of left atrial appendage chymase gene transcripts and chymase activity, but no differences in angiotensinogen mRNA. Atrial chymase enzymatic activity was highly correlated with left atrial but not right atrial enlargement as determined by echocardiography, while both tyrosine hydroxylase and neuropeptide Y atrial appendage mRNAs correlated with atrial angiotensinogen mRNAs. CONCLUSIONS: Higher Ang-(1-12) expression and upregulation of chymase gene transcripts and enzymatic activity from the atrial appendages connected to the enlarged left versus right atrial chambers of subjects with left heart disease defines a role of this alternate Ang II forming pathway in the processes accompanying adverse atrial and ventricular remodeling.
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Authors: Carlos M Ferrario; Sarfaraz Ahmad; Jasmina Varagic; Che Ping Cheng; Leanne Groban; Hao Wang; James F Collawn; Louis J Dell Italia Journal: Am J Physiol Heart Circ Physiol Date: 2016-05-27 Impact factor: 4.733
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