Details

Autor(en) / Beteiligte

• Deng, Wei
• Ednie, Andrew
• Bennett, Eric

Titel

Partial Reduction in Cardiac Sialylation Contributes to Dilated Cardiomyopathy and Heart Failure

Ist Teil von

• The FASEB journal, 2015-04, Vol.29 (S1)

Erscheinungsjahr

2015

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Abstract only Dilated cardiomyopathy (DCM) leads to heart failure (HF) and is often associated with life‐threatening arrhythmias. Protein glycosylation is altered in DCM and with DCM risk factors. Patients with congenital disorders of glycosylation often present with DCM and related arrhythmias. We previously showed that gene deletion of the sialyltransferase, ST3Gal4, results in partial reduction in cardiac sialylation, altered cardiac Na v gating, and increased susceptibility to arrhythmias. Here, we investigated the impact of ST3Gal4 gene deletion on cardiac performance. Anomalous ECGs, including prolonged QT and corrected QT intervals, were recorded in ST3Gal4 ‐/‐ male mice. One‐year old ST3Gal4 ‐/‐ mice developed left ventricle (LV) dilation as evidenced by significantly increased LV end‐diastolic volume (EDV) and a significantly thinner LV posterior wall compared to wild type (WT). Transverse aortic constriction (TAC) was used as a stressor on 16‐20 week old animals. TAC'd ST3Gal4 ‐/‐ hearts decompensated rapidly, presenting by week 3 post‐surgery with significant LV dilation and reduced systolic function (together indicating HF) compared to TAC'd WT littermates (ejection fraction, EF%, ST3Gal4 ‐/‐ = 35.3 ± 3.6%, WT = 48.3 ± 3.5%, p<0.05; EDV(µl), ST3Gal4 ‐/‐ = 103 ± 4.6, WT = 79 ± 5.7, n = 7‐10; p<0.01). Thus, gene deletion of ST3Gal4 results in aberrant electrical signaling and to the later onset of apparent DCM. The DCM phenotype was more pronounced with stress in ST3Gal4 ‐/‐ mice, presenting with HF by week three following pressure‐overload induction. Thus, partial reduction of sialylation contributes to aberrant cardiac electrical signaling and performance with the functional phenotype exacerbated under stress conditions that lead to the rapid onset of HF.