Protein Kinase Beta II (PKC-βІI) inhibitor exerts cardioprotective effects in Myocardial Ischemia/Reperfusion Injury (MI/R)
Date of Award
Master of Science in Biomedical Sciences
Lindon Young, PhD
Qian Chen, PhD
Cathy Hatcher, PhD
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 or 20μM) will attenuate infarct size and improve post-reperfused cardiac function compared to untreated controls in isolated perfused rat hearts subjected to I(30min)/R(90 min). PKC βII- treated hearts (both 10 and 20 μM) significantly improved postreperfused cardiac function (e.g. left ventricular developed pressure [LVDP], and dP/dt max) compared to controls (all p<0.05). I/R+PKC βII inhibitor hearts (10 μM , n=7; 20 μM, n=5) exhibited a significant improvement in LVDP 66 + 8% mmHg, and dP/dt max 56 + 8%mmHg/s (20 μM) and 57±7% mmHg, 48±5% mmHg/s (10 μM) compared to control I/R hearts (n=9) that only recovered to 38±6% mmHg and 28 ±4% mmHg/s at 90 min post-reperfusion of initial baseline. Additionally, the 20 μM PKC βII- treated hearts significantly restored post-reperfused LVDP as early as 10min postreperfusion as this effect is attributed to significantly better LV end diastolic pressure compared to controls (both p<0.05). Regarding heart tissue viablity, PKC βII- treated hearts showed significant reduction in infarct size (25±3% [20 μM] and 29±3% [10 μM]) compared to controls (46±3%) [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.
Lipscombe, Christina G., "Protein Kinase Beta II (PKC-βІI) inhibitor exerts cardioprotective effects in Myocardial Ischemia/Reperfusion Injury (MI/R)" (2019). PCOM Biomedical Studies Student Scholarship. 175.