Thorac Cardiovasc Surg 2010; 58 - MP53
DOI: 10.1055/s-0029-1246862

Identifying PKC epsilon as a target molecule to control intimal hyperplasia

S Schrepfer 1, T Deuse 2, 3, T Koyanagi 4, H Reichenspurner 2, RC Robbins 3, D Mochly-Rosen 4
  • 1Stanford University, Cardiothoracic Surgery, Stanford, United States
  • 2Universitäres Herzzentrum Hamburg, Herzchirurgie, TSI-Lab, Hamburg, Germany
  • 3Stanford University School of Medicine, CT Surgery, Stanford, United States
  • 4Stanford University School of Medicine, Pharmacology, Stanford, United States

Background: Epsilon protein kinase C (εPKC) is a PKC isoform that plays pivotal roles in myocardial infarction and in heart failure. Here we investigate whether PKC epsilon activation is also involved in the development of intimal hyperplasia.

Methods: Rats underwent balloon denudation of the abdominal aorta and received either 3mM εPKC activator (yeRACK), 3mM εPKC inhibitor (εV1–2), the carrier control (TAT47–57), or saline by osmotic pump at ˜3mg/kg/day for 4 weeks (6 rats/group). Aortas were harvested for histologic evaluation, and luminal obliteration and intima/media ratios were analyzed using computer morphometry.

Results: Histology of untreated animals revealed marked intimal hyperplasia with moderate luminal obliteration (19.9±9%). Neointima formation was significantly increased by the εPKC activator (32±5.5%; p=0.017 vs. untreated) and significantly decreased by the εPKC inhibitor (9.1±4.3%; p=0.016 vs. untreated). No difference was observed between the untreated control and the TAT carrier peptide contol groups (p=0.43). The intima/media ratio was significantly higher in the εPKC activator group compared to the εPKC inhibitor group (0.67±0.46 and 0.25±0.46, respectively; p=0.034). Treatment with either of the ePKC regulators was very well tolerated. No differences in creatinine, BUN, cholesterol, triglycerides, ALT, and AST were observed between the four groups.

Conclusion: These data suggest that εPKC activity contributes to the non-immunological development of intimal hyperplasia and that an εPKC-selective inhibitor, such as εV1–2, could augment current therapeutic strategies to suppress the development of vascular stenosis.