Journal
CARDIOVASCULAR RESEARCH
Volume 91, Issue 3, Pages 447-455Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvr106
Keywords
Endoplasmic reticulum; Heart failure; Calcium handling; Stress; Apoptosis
Categories
Funding
- Science and Technology Commission of Shanghai, P. R. China [08431903002]
Ask authors/readers for more resources
Aims Alterations in calcium homeostasis in the endoplasmic/sarcoplasmic reticulum (ER) cause ER stress that ultimately may affect ventricular function. However, the role of ER stress in beta-blocker therapy for congestive heart failure (CHF) has not been studied. This study examined ER stress in CHF and evaluated its role in b-blocker therapy in a canine model of ischaemic CHF. Methods and results CHF was created by daily coronary embolization in chronically instrumented dogs. After oral administration of beta-blocker metoprolol or vehicle for 12 weeks, Ca2+ transport proteins including sarcoplasmic reticulum Ca2+-ATPase (SERCA), ryanodine receptor (RyR2), Na+-Ca2+ exchanger (NCX1), Ca2+ storage protein calreticulin (CRT), and phospholamban were evaluated by Western blot analysis. Cellular levels of ER stress marker, phosphorylated eukaryotic initiation factor 2 alpha (eIF2 alpha-P), were also examined. Compared with the vehicle-treated group, metoprolol caused significantly improved cardiac function, restored the proteins of SERCA2a, NCX1, and CRT, increased phosphorylated phospholamban, reversed protein kinase A hyperphosphorylation of RyR2, and resulted in normalized ER stress marker eIF2a-P and reduced DNA damage. Conclusions Our results suggest that ER stress could be induced by abnormal Ca2+ homeostasis in CHF. The restoration of calcium-handling protein function and resultant decrease in ER stress might, in part, explain the beneficial effects of beta-blockade observed in CHF. Whether this mechanism occurs in other animal CHF models or human CHF warrants further study.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available