TRAM‐34 coated balloons prevent smooth muscle phenotypic modulation following porcine coronary angioplasty

We previously demonstrated in vivo upregulation of intermediate‐conductance Ca 2+ ‐activated K + channel (IKCa1) in medial smooth muscle cells 2 hours following coronary balloon angioplasty. IKCa1 upregulation preceded the downregulation of smooth muscle myosin heavy chain (SMMHC), which occurred 2 days following angioplasty. We also demonstrated in vitro that TRAM‐34, a specific IKCa1 blocker, prevented platelet‐derived growth factor BB (PDGF‐BB)‐induced upregulation of IKCa1, as well as downregulation of smooth muscle specific marker genes, thus smooth muscle phenotypic modulation. In the current study, we tested the hypothesis that blockade of IKCa1 with TRAM‐34 would prevent upregulation of IKCa1 and smooth muscle phenotypic modulation following angioplasty. TRAM‐34 was delivered by subcutaneous injection or coated onto balloons. Balloons were coated 3 times with TRAM‐34 (20mg/mL in acetone) by submersion for 10 sec. followed by drying for 1 min. TRAM‐34 coated balloons prevented the upregulation of IKCa1 mRNA 2 hours after angioplasty, as well as prevented the downregulation of SMMHC mRNA 2 days after angioplasty, as determined by quantitative RT‐PCR. Subcutaneous injection of TRAM‐34 (1.8 g in peanut oil) had no effect. In conclusion, local blockade of IKCa1 prevented IKCa1 upregulation and the acute onset of coronary smooth muscle phenotypic modulation following coronary angioplasty. Supported by: NIH HL52490