| First Author | Hu Z | Year | 2014 |
| Journal | Circ Cardiovasc Genet | Volume | 7 |
| Issue | 1 | Pages | 33-42 |
| PubMed ID | 24403551 | Mgi Jnum | J:320829 |
| Mgi Id | MGI:6837430 | Doi | 10.1161/CIRCGENETICS.113.000315 |
| Citation | Hu Z, et al. (2014) Kcne2 deletion creates a multisystem syndrome predisposing to sudden cardiac death. Circ Cardiovasc Genet 7(1):33-42 |
| abstractText | BACKGROUND: Sudden cardiac death (SCD) is the leading global cause of mortality, exhibiting increased incidence in patients with diabetes mellitus. Ion channel gene perturbations provide a well-established ventricular arrhythmogenic substrate for SCD. However, most arrhythmia-susceptibility genes, including the KCNE2 K(+) channel beta subunit, are expressed in multiple tissues, suggesting potential multiplex SCD substrates. METHODS AND RESULTS: Using whole-transcript transcriptomics, we uncovered cardiac angiotensinogen upregulation and remodeling of cardiac angiotensinogen interaction networks in P21 Kcne2(-/-) mouse pups and adrenal remodeling consistent with metabolic syndrome in adult Kcne2(-/-) mice. This led to the discovery that Kcne2 disruption causes multiple acknowledged SCD substrates of extracardiac origin: diabetes mellitus, hypercholesterolemia, hyperkalemia, anemia, and elevated angiotensin II. Kcne2 deletion was also a prerequisite for aging-dependent QT prolongation, ventricular fibrillation and SCD immediately after transient ischemia, and fasting-dependent hypoglycemia, myocardial ischemia, and AV block. CONCLUSIONS: Disruption of a single, widely expressed arrhythmia-susceptibility gene can generate a multisystem syndrome comprising manifold electric and systemic substrates and triggers of SCD. This paradigm is expected to apply to other arrhythmia-susceptibility genes, the majority of which encode ubiquitously expressed ion channel subunits or regulatory proteins. |
