Effects of local delivery of tetradecylthioacetic acid within the injured coronary vessel wall

Scand Cardiovasc J. 2012 Dec;46(6):366-73. doi: 10.3109/14017431.2012.725477. Epub 2012 Sep 25.

Abstract

Objectives: Inflammation is involved in cell proliferation and collagen deposition causing vessel wall remodeling and restenosis after plain balloon angioplasty. Local drug delivery of bioactive agents that reduce the incidence of adverse wall remodeling is of considerable interest concerning treatment strategies for coronary vessel disease and could alter the need of repeated revascularization.

Design: In this study, 34 domestic pigs undergoing coronary balloon injury were randomly assigned to Tetradecylthioacetic acid (TTA) or placebo delivered locally. After four weeks, vessel wall collagen density, inflammatory markers and lipid fractions were assessed as well as cell proliferation.

Results: Collagen particle count was lower after TTA compared to placebo, 177 ± 11 n/area versus 225 ± 13 n/area (p = 0.007). Interleukin-2 (IL-2) concentration was reduced, 1.6 ± 0.02 pg/ml versus 2.6 ± 0.5 pg/ml, (p = 0.01). The anti-inflammatory index was increased after TTA, 46.28 ± 12.1 versus 34.66 ± 4.5, (p = 0.025). There were no differences between TTA and placebo with regard to cell proliferation.

Conclusions: Local delivery of TTA reduced the local inflammatory response and collagen accumulation. Local balloon delivery of TTA into the vessel wall may represent an alternative antiproliferative strategy for preventing restenosis, in particular for vessels with obstructive disease not available for stent implantation.

MeSH terms

  • Angioplasty, Balloon, Coronary
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Cardiac Catheters
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Coronary Restenosis / etiology
  • Coronary Restenosis / metabolism
  • Coronary Restenosis / pathology
  • Coronary Restenosis / prevention & control*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / injuries*
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Drug Delivery Systems* / instrumentation
  • Female
  • Inflammation Mediators / metabolism
  • Interleukin-2 / metabolism
  • Lipid Metabolism / drug effects
  • Male
  • Sulfides / administration & dosage*
  • Sus scrofa
  • Time Factors
  • Vascular System Injuries / drug therapy*
  • Vascular System Injuries / etiology
  • Vascular System Injuries / metabolism
  • Vascular System Injuries / pathology

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Interleukin-2
  • Sulfides
  • 1-(carboxymethylthio)tetradecane
  • Collagen