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Presentation
Protein kinase C beta II (PKC ßII) peptide inhibitor exerts cardioprotective effects in myocardial ischemia/reperfusion injury
Research Day
  • Christina Lipscombe, Philadelphia College of Osteopathic Medicine
  • Israel Benjamin
  • Devon Stutzman
  • Amelie Bottex
  • Chinyere Ebo
  • Qian Chen
  • Robert Barsotti
Location
Philadelphia
Start Date
11-5-2016 1:00 PM
Description
During myocardial ischemia/reperfusion (I/R), the generation of reactive oxygen species (ROS) contributes to the post-reperfused cardiac injury and contractile dysfunction. Activation of Protein Kinase C beta II (PKC βII) has been associated with increased ROS release from myocardial I/R tissue, decreased endothelial-derived nitric oxide, and increased infarct size. We tested the hypothesis that using a cell permeable PKC βII peptide inhibitor (PKC βII-) (N-myr-SLNPEWNET, MW=1300 g/mol, 10µM) will attenuate infarct size and improve post-reperfused cardiac function compared to untreated controls in isolated perfused rat hearts subjected to I(30min)/R(45 or 90 min). The 90 min reperfusion group (n=9) showed significantly less recovery to the initial baselines in left ventricular developed pressure (LVDP) (38±6%) and maximal rate of LVDP (+dP/dtmax ) (28±4%), both p˂0.01. The 45 min reperfusion group (n=9) also showed significantly compromised LVDP (46±6%) and +dP/dtmax (35±4%) compared to initial baseline but to a lesser extent than the 90 min group. Conversely, PKC βII- treated hearts significantlyimproved cardiac function compared to controls (all p<0.05). Similarly, 90 min reperfusion (n=7) showed a reduced recovery in LVDP (57±7%) and +dP/dtmax (48±5%) compared to 45 min reperfusion (LVDP: 70±6%; +dP/dtmax: 55±6%; n=7). Furthermore, PKC βII- treated hearts showed significant reduction in infarct size (24±3% and 29±3% for 45 and 90 min reperfusion, respectively) compared to controls (43±2% and 46±3% for 45 and 90 min reperfusion, respectively; [p˂0.01]). The results suggest that PKC βII- is effective in improving cardiac function and reducing infarct size and aids in clinical myocardial infarction/organ transplantation patient recovery.
Citation Information
Christina Lipscombe, Israel Benjamin, Devon Stutzman, Amelie Bottex, et al.. "Protein kinase C beta II (PKC ßII) peptide inhibitor exerts cardioprotective effects in myocardial ischemia/reperfusion injury" (2016)
Available at: http://works.bepress.com/qian_chen/51/