Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium

Nancy S. Saad, Mohammad T. Elnakish, Elizabeth A. Brundage, Brandon J. Biesiadecki, Ahmet Kilic, Amany A.E. Ahmed, Peter J. Mohler, Paul M.L. Janssen

Research output: Contribution to journalArticle

Abstract

Aims: Heart failure (HF) is a prevalent disease that is considered the foremost reason for hospitalization in the United States. Most protein kinases (PK) are activated in heart disease and their inhibition has been shown to improve cardiac function in both animal and human studies. However, little is known about the direct impact of PKA and PKC inhibitors on human cardiac contractile function. Material and methods: We investigated the ex vivo effect of such inhibitors on force as well as on kinetics of left ventricular (LV) trabeculae dissected from non-failing and failing human hearts. In these experiments, we applied 0.5 μM of H-89 and GF109203X, which are PKA and PKC inhibitors, respectively, in comparison to their vehicle DMSO (0.05%). Key findings and conclusion: Statistical analyses revealed no significant effect for H-89 and GF109203X on either contractile force or kinetics parameters of both non-failing and failing muscles even though they were used at a concentration higher than the reported IC50s and Kis. Therefore, several factors such as selectivity, concentration, and treatment time, which are related to these PK inhibitors according to previous studies require further exploration.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalLife Sciences
Volume215
DOIs
StatePublished - Dec 15 2018
Externally publishedYes

Fingerprint

Myocardium
Kinetics
Protein Kinase Inhibitors
Dimethyl Sulfoxide
Kinetic parameters
Protein Kinases
Muscle
Heart Diseases
Animals
Hospitalization
Heart Failure
Muscles
protein kinase modulator
Experiments
bisindolylmaleimide I
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
Therapeutics

Keywords

  • Contractility
  • Force
  • Force-frequency
  • Human heart
  • PKA
  • Trabeculae

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Saad, N. S., Elnakish, M. T., Brundage, E. A., Biesiadecki, B. J., Kilic, A., Ahmed, A. A. E., ... Janssen, P. M. L. (2018). Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium. Life Sciences, 215, 119-127. https://doi.org/10.1016/j.lfs.2018.10.065

Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium. / Saad, Nancy S.; Elnakish, Mohammad T.; Brundage, Elizabeth A.; Biesiadecki, Brandon J.; Kilic, Ahmet; Ahmed, Amany A.E.; Mohler, Peter J.; Janssen, Paul M.L.

In: Life Sciences, Vol. 215, 15.12.2018, p. 119-127.

Research output: Contribution to journalArticle

Saad, NS, Elnakish, MT, Brundage, EA, Biesiadecki, BJ, Kilic, A, Ahmed, AAE, Mohler, PJ & Janssen, PML 2018, 'Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium', Life Sciences, vol. 215, pp. 119-127. https://doi.org/10.1016/j.lfs.2018.10.065
Saad, Nancy S. ; Elnakish, Mohammad T. ; Brundage, Elizabeth A. ; Biesiadecki, Brandon J. ; Kilic, Ahmet ; Ahmed, Amany A.E. ; Mohler, Peter J. ; Janssen, Paul M.L. / Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium. In: Life Sciences. 2018 ; Vol. 215. pp. 119-127.
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