Journal
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Volume 70, Issue 6, Pages 447-462Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1369/00221554221101661
Keywords
aging; arrhythmia; connexin phosphorylation; EEG; electrical activity; heart function; insulin resistance; metabolic syndrome
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Funding
- Scientific and Technological Research Council of Turkey [SGAB119S661]
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This study demonstrated a correlation between long-QT and connexin 43 (Cx43) status and localization in elderly rats, showing the important role of insulin resistance (I-R), ischemia-reperfusion, aging, and heart dysfunction. Alterations in Cx43 protein level and localizations in aging heart were found to lead to abnormal ventricular repolarization in I-R heart.
The correlation between long-QT and connexin 43 (Cx43) status and localization in elderly rats was determined to demonstrate a correlation between insulin resistance (I-R), ischemia-reperfusion, aging, and heart dysfunction. Male Wistar rats are grouped as 24-month-old rats (Aged-group), those with metabolic syndrome (8 months old; MetS-group), or controls (8 months old; Con-group). Both experimental groups have long-QT and low heart rate. Immunohistochemical imaging and quantification showed marked decreases in Cx43 staining of intercalated disc with less localizations in the Aged-group and MetS-group. The lateralization of Cx43 on longitudinal cell membrane was significantly high in the MetS-group than in the Con-group with no significant change in the Aged-group. Its significant cytoplasmic internalization was higher in the Aged-group than in the MetS-group. There were marked decreases in phospho-Cx43 (pCx43) staining of intercalated disc with less localizations in both groups than in the Con-group. Furthermore, lateralization of pCx43 was significantly low in the Aged-group and MetS-group, whereas there were no significant changes in the cytoplasmic internalization of both groups compared with the Con-group. Furthermore, the ratio of pCx43 to Cx43 was significantly small in both groups. We determined increases in RhoA and endothelin-1 in both groups, further supporting decreases in pCx43. Our data indicate the important role of I-R on long-QT in aging heart through alterations in both Cx43 protein level and localizations, leading to an abnormal spreading of ventricular repolarization in I-R heart:
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