Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins
| Autor: | Paul Hales, Nancy E. Stagliano, Colin T. Maguire, Jian Xu, Roger E. Breitbart, Vivek J. Kadambi, Charles I. Berul, Victoria Fairchild-Huntress, Mary Donoghue, John N. Lorenz, Hiroko Wakimoto, Susan L. Acton |
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| Rok vydání: | 2003 |
| Předmět: |
Tachycardia
medicine.medical_specialty Connexin Down-Regulation Gene Expression Mice Transgenic Carboxypeptidases Peptidyl-Dipeptidase A Ventricular tachycardia Sudden death Connexins Gene Expression Regulation Enzymologic Death Sudden Electrocardiography Mice Internal medicine medicine Animals Transgenes Ventricular remodeling Molecular Biology biology Angiotensin-converting enzyme Arrhythmias Cardiac medicine.disease Electrophysiology Endocrinology Heart Block Connexin 43 Angiotensin-converting enzyme 2 Ventricular fibrillation Ventricular Fibrillation cardiovascular system biology.protein Cardiology Tachycardia Ventricular Angiotensin-Converting Enzyme 2 medicine.symptom Cardiology and Cardiovascular Medicine hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of molecular and cellular cardiology. 35(9) |
| ISSN: | 0022-2828 |
| Popis: | Angiotensin converting enzyme related carboxypeptidase (ACE2) is a recently discovered homolog of angiotensin converting enzyme with tissue-restricted expression, including heart, and the capacity to cleave angiotensin peptides. We tested the hypothesis that cardiac ACE2 activity contributes to features of ventricular remodeling associated with the renin-angiotensin system by generating transgenic mice with increased cardiac ACE2 expression. These animals had a high incidence of sudden death that correlated with transgene expression levels. Detailed electrophysiology revealed severe, progressive conduction and rhythm disturbances with sustained ventricular tachycardia and terminal ventricular fibrillation. The gap junction proteins connexin40 and connexin43 were downregulated in the transgenic hearts, indicating that ACE2-mediated gap junction remodeling may account for the observed electrophysiologic disturbances. Spontaneous downregulation of the ACE2 transgene in surviving older animals correlated with restoration of nearly normal conduction, rhythm, and connexin expression. |
| Databáze: | OpenAIRE |
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