Delivery of the KCa3.1 blocker TRAM-34 via coated balloon catheter prevented smooth muscle phenotypic modulation and reduced postangioplasty restenosis by 38% at 14 days and 22% at 28 days.
Does local delivery of the KCa3.1 blocker TRAM-34 via coated balloon prevent smooth muscle phenotypic modulation and limit restenosis in a swine model of postangioplasty?
Local delivery of the KCa3.1 blocker TRAM-34 via balloon catheter prevents acute smooth muscle phenotypic modulation and reduces subsequent restenosis in a preclinical swine model.
p-value: p=<0.05
OBJECTIVE: We previously demonstrated that upregulation of intermediate-conductance Ca(2+)-activated K(+) channels (K(Ca)3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of K(Ca)3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis. METHODS AND RESULTS: Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific K(Ca)3.1 blocker TRAM-34. Expression of K(Ca)3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. K(Ca)3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented K(Ca)3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level. CONCLUSIONS: Blockade of K(Ca)3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis.
Tharp et al. (2008) studied Postangioplasty restenosis (n=20). TRAM-34 coated balloon catheter vs. Noncoated balloon catheter was evaluated on Postangioplasty restenosis (normalized intimal to medial thickness ratio) (p=<0.05). Delivery of the KCa3.1 blocker TRAM-34 via coated balloon catheter prevented smooth muscle phenotypic modulation and reduced postangioplasty restenosis by 38% at 14 days and 22% at 28 days.