Abstract
INTRODUCTION: Dual conjugation of PKC Beta II peptide inhibitor (PKCβII-) with myristic acid (myr) and trans-activator of transcription (Tat) (Myr-Tat-CC-SLNPEWNET [myr-Tat-PKCβII-]) has been shown to enhance intracellular delivery and attenuate myocardial ischemia/reperfusion (I/R) injury in an ex-vivo rat model. Previously, myr-Tat-PKCβII- demonstrated significant cardioprotective effects from 100nM to the 1pM concentration.
OBJECTIVES: The lowest concentration at which myr-Tat-PKCβII- is still cardioprotective has yet to be determined; this study investigates the 100fM concentration.
METHODS: Isolated rat hearts from anesthetized male SD rats (275g to 300g) underwent global I(30-min)/R(50-min). Cardiac function was recorded via a pressure transducer. Treatments were infused during the first 5 min of R. Following R, infarct size was determined by excising infarcted tissue stained with 1% triphenyltetrazolium chloride (i.e. infarct tissue weight/ total tissue weight). Data were analyzed using ANOVA Fisher’s LSD analysis.
RESULTS: For both infarct size and final +dP/dt Max, myr-Tat-PKCβII- 100fM (12.1±0.9%, 401±60mmHg/s, n=3) was not significantly different compared to untreated controls (21.9±2.8%, 783±92mmHg/s, n=20). Compared to the 1pM concentration (1095±433mmHg/s, n=4), final +dP/dt Max at 100fM was significantly depressed (p<0.05).
CONCLUSION: Myr-Tat-PKCβII- 100fM demonstrated a reduction in infarct size accompanied with cardiac depression. Although this reduction in infarct size was not significant compared to untreated controls, further testing is required due to the small sample size (n=3). Myr-Tat-PKCβII- has continually exhibited concentration-independent reduction in infarct size, by an unknown mechanism. However, thus far in our ongoing experiments, cardiac function has been concentration-dependent with optimal function at 1pM and depressed function at both extremes (i.e., 100nM and 100fM). Future studies will continue to test the 100fM concentration to evaluate the effect of myr-Tat-PKCβ- on infarct size and heart function. Lower concentrations of myr-Tat-PKCβ- in the lower fM range will be tested if needed.
Original language | American English |
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State | Published - May 3 2023 |
Keywords
- Cardiac
- Ischemia
- Myr-Tat
- PKC Beta
- Reperfusion
Disciplines
- Cardiology
- Medicine and Health Sciences