Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis
| Autor: | Alex Cheong, Darla L. Tharp, B. R. Wamhoff, Heike Wulff, D. K. Bowles, Girija Raman |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Proto-Oncogene Proteins c-jun Swine medicine.medical_treatment Article Muscle Smooth Vascular Andrology Downregulation and upregulation Restenosis Angioplasty medicine Potassium Channel Blockers Animals Angioplasty Balloon Coronary business.industry Balloon catheter Coronary Stenosis Potassium channel blocker Cell Differentiation medicine.disease Intermediate-Conductance Calcium-Activated Potassium Channels Coronary Vessels Surgery Coronary arteries Stenosis Disease Models Animal medicine.anatomical_structure Phenotype Myocardin Pyrazoles Cardiology and Cardiovascular Medicine business Proto-Oncogene Proteins c-fos medicine.drug Transcription Factors |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 28(6) |
| ISSN: | 1524-4636 |
| Popis: | 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. Conclusion— Blockade of K Ca 3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis. |
| Databáze: | OpenAIRE |
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