Potential role of cartilage oligomeric matrix protein in the modulation of pulmonary arterial smooth muscle superoxide by hypoxia

American Journal of Physiology. Lung Cellular and Molecular Physiology
Hang YuMichael S Wolin

Abstract

Changes in reactive oxygen species and extracellular matrix seem to participate in pulmonary hypertension development. Because we recently reported evidence for chronic hypoxia decreasing expression of cartilage oligomeric matrix protein (COMP) and evidence for this controlling loss of pulmonary arterial smooth muscle bone morphogenetic protein receptor-2 (BMPR2) and contractile phenotype proteins, we examined if changes in superoxide metabolism could be an important factor in a bovine pulmonary artery (BPA), organoid cultured under hypoxia for 48 h model. Hypoxia (3% O2) caused a depletion of COMP in BPA, but not in bovine coronary arteries. Knockdown of COMP by small-interfering RNA (siRNA) increased BPA levels of mitochondrial and extra-mitochondrial superoxide detected by MitoSOX and dihydroethidium (DHE) HPLC products. COMP siRNA-treated BPA showed reduced levels of SOD2 and SOD3 and increased levels of NADPH oxidases NOX2 and NOX4. Hypoxia increased BPA levels of MitoSOX-detected superoxide and caused changes in NOX2 and SOD2 expression similar to COMP siRNA, and exogenous COMP (0.5 μM) prevented the effects of hypoxia. In the presence of COMP, BMPR2 siRNA-treated BPA showed increases in superoxide detected by MitoSOX and...Continue Reading

References

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Apr 3, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Dhara PatelMichael S Wolin

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Citations

Mar 14, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Ghezal FrooghAn Huang
Apr 15, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Adam M Wegner, Dominik R Haudenschild
Aug 31, 2021·Oxidative Medicine and Cellular Longevity·Cuilan HouTingting Xiao

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Methods Mentioned

BETA
electrophoresis
transfection

Software Mentioned

GraphPad Prism
SCAN
UN
IT gel

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