Skip to main content
padlock icon - secure page this page is secure

Pleiotropic Effects of Simvastatin on Some Calcium Regulatory and Myofibrillar Proteins in Ischemic/Reperfused Heart: Causality of Statins Cardioprotection?

Buy Article:

$68.00 + tax (Refund Policy)

Background: It is known that statins possess beneficial cardioprotective effects irrespective of lipidlowering action and that cardiac injury due ischemia/reperfusion is associated with Ca2+ dysregulation resulting in contractile dysfunction.

Objective: With this background, we tested a hypothesis that simvastatin influences signaling of Ca2+/calmodulindependent protein kinase IIδ (CaMKIIδ), a protein kinase regulating both Ca2+ homeostasis and thick filament function, and thereby might underlie the mitigation of ischemia/reperfusion (I/R)-induced cardiac dysfunction.

Method: Isolated hearts of control and simvastatin-treated (p.o. 10 mg/kg, 5 days) rats were subjected to global I and R and Western blotting was used to study the expression/activation of certain signaling proteins.

Results: Simvastatin treatment did not modify the plasma lipid levels; however, it recovered depressed cardiac performance and reduced reperfusion arrhythmias without affecting the activation of CaMKIIδ through phosphorylation of Thr287. Activation of its downstreams, such as phospholamban (PLN) and cardiac myosin-binding protein C (cMyBP-C) at Thr17 and Ser282, respectively, was in accordance with the levels of pThr287-CaMKIIδ. Total expression of these proteins, however, did not follow the same pattern and was either unchanged (CaMKIIδ, cMYBP-C) or increased (PLN). Likewise, PLN/SERCA2a (sarco/endoplasmic reticulum Ca2+-ATPase 2a) ratio in I/R hearts was unaffected by the treatment. On the other hand, simvastatin reversed the increased protein expression of protein phosphatase 1β (PP1β), but not protein phosphatase 2A (PP2A), in I/R hearts.

Conclusion: A lower rate of dephosphorylation and thereby a delay in inactivation of phosphorylated proteins due to a decrease in PP1β, rather than effects on phosphorylation of CaMKIIδ and its downstreams, such as PLN and cMyBP-C, may underlie beneficial effects of simvastatin in I/R hearts.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: CaMKII; Ischemia-reperfusion; cMyBP-C; heart; protein phosphatase; simvastatin

Document Type: Research Article

Publication date: November 1, 2016

More about this publication?
  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
  • Editorial Board
  • Information for Authors
  • Subscribe to this Title
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more