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Journal article
Mechanotransduction Drives Post Ischemic Revascularization Through K-ATP Channel Closure and Production of Reactive Oxygen Species
Antioxidants & redox signaling, v 20(6), pp 872-886
20 Feb 2014
PMID: 23758611
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aims: We reported earlier that ischemia results in the generation of reactive oxygen species (ROS) via the closure of a K-ATP channel which causes membrane depolarization and NADPH oxidase 2 (NOX2) activation. This study was undertaken to understand the role of ischemia-mediated ROS in signaling. Results: Angiogenic potential of pulmonary microvascular endothelial cells (PMVEC) was studied in vitro and in the hind limb in vivo. Flow adapted PMVEC injected into a Matrigel matrix showed significantly higher tube formation than cells grown under static conditions or cells from mice with knockout of K-ATP channels or the NOX2. Blocking of hypoxia inducible factor-1 alpha (HIF-1) accumulation completely abrogated the tube formation in wild-type (WT) PMVEC. With ischemia in vivo (femoral artery ligation), revascularization was high in WT mice and was significantly decreased in mice with knockout of K-ATP channel and in mice orally fed with a K-ATP channel agonist. In transgenic mice with endothelial-specific NOX2 expression, the revascularization observed was intermediate between that of WT and knockout of K-ATP channel or NOX2. Increased HIF-1 activation and vascular endothelial growth factor (VEGF) expression was observed in ischemic tissue of WT mice but not in K-ATP channel and NOX2 null mice. Revascularization could be partially rescued in K-ATP channel null mice by delivering VEGF into the hind limb. Innovation: This is the first report of a mechanosensitive ion channel (K-ATP channel) initiating endothelial signaling that drives revascularization. Conclusion: The K-ATP channel responds to the stop of flow and activates signals for revascularization to restore the impeded blood flow.
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Details
- Title
- Mechanotransduction Drives Post Ischemic Revascularization Through K-ATP Channel Closure and Production of Reactive Oxygen Species
- Creators
- Elizabeth Browning - University of PennsylvaniaHui Wang - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USANankang Hong - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USAKevin Yu - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USADonald G. Buerk - Drexel UniversityKristine DeBolt - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USADaniel Gonder - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USAElena M. Sorokina - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USAPuja Patel - Childrens Hosp Philadelphia, Div Endocrinol Diabet, Philadelphia, PA 19104 USADiva D. De Leon - Childrens Hosp Philadelphia, Div Endocrinol Diabet, Philadelphia, PA 19104 USASheldon I. Feinstein - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USAAron B. Fisher - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USAShampa Chatterjee - Univ Penn, Inst Environm Med, Perelman Sch Med, Philadelphia, PA 19104 USA
- Publication Details
- Antioxidants & redox signaling, v 20(6), pp 872-886
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 15
- Grant note
- R01HL-075587 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA McCabe Foundation Award T32HL007748 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000331289900003
- Scopus ID
- 2-s2.0-84893858139
- Other Identifier
- 991019169656904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Endocrinology & Metabolism