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Göteborgs universitets publikationer

Protein disulfide isomerase increases in myocardial endothelial cells in mice exposed to chronic hypoxia: a stimulatory role in angiogenesis.

Författare och institution:
Fei Tian (Institutionen för medicin, avdelningen för molekylär och klinisk medicin & Wallenberglaboratoriet); Xianghua Zhou (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Johannes Wikström (-); Helen Karlsson (-); Helen Sjöland (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Li-Ming Gan (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Jan Borén (Institutionen för medicin, avdelningen för molekylär och klinisk medicin & Wallenberglaboratoriet); Levent Akyürek (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi)
Publicerad i:
American journal of physiology. Heart and circulatory physiology, 297 ( 3 ) s. H1078-86
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Previous studies have shown that exposure to chronic hypoxia protects against myocardial infarction, but little is known about the cellular and molecular mechanisms involved. Here we observed that chronic hypoxia for 3 wk resulted in improved survival of mice (from 64% to 83%), reduced infarction size (from 45 +/- 4% to 32 +/- 4%, P < 0.05), increased cardiac ejection fraction (from 19 +/- 4% to 35 +/- 5%, P < 0.05), coronary flow velocity under adenosine-induced hyperemia (from 58 +/- 2 to 75 +/- 5 cm/s, P < 0.05), myocardial capillary density (from 3,772 +/- 162 to 4,760 +/- 197 capillaries/mm(2), P < 0.01), and arteriolar density (from 8.04 +/- 0.76 to 10.34 +/- 0.69 arterioles/mm(2), P < 0.05) 3 wk after myocardial infarction. With two-dimensional gel electrophoresis, we identified that protein disulfide isomerase (PDI) was highly upregulated in hypoxic myocardial capillary endothelial cells. The loss of PDI function in endothelial cells by small interfering RNA significantly increased the number of apoptotic cells (by 3.4-fold at hypoxia, P < 0.01) and reduced migration (by 52% at hypoxia, P < 0.001) and adhesion to collagen I (by 42% at hypoxia, P < 0.01). In addition, the specific inhibition of PDI by PDI small interfering RNA (by 46%, P < 0.01) and bacitracin (by 72%, P < 0.001) reduced the formation of tubular structures by endothelial cells. Our data indicate that chronic hypoxic exposure improves coronary blood flow and protects the myocardium against infarction. These beneficial effects may be partly explained by the increased endothelial expression of PDI, which protects cells against apoptosis and increases cellular migration, adhesion, and tubular formation. The increased PDI expression in endothelial cells may be a novel mechanism to protect the myocardium against myocardial ischemic diseases.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Cell- och molekylärbiologi
Animals, Anoxia, metabolism, pathology, physiopathology, Apoptosis, physiology, Arterioles, physiology, Body Weight, Capillaries, physiology, Cell Adhesion, physiology, Cell Movement, physiology, Cells, Cultured, Chronic Disease, Coronary Circulation, physiology, Endothelial Cells, cytology, enzymology, Hemoglobins, metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Myocardial Infarction, metabolism, pathology, physiopathology, Neovascularization, Physiologic, physiology, Organ Size, Protein Disulfide-Isomerases, genetics, metabolism, RNA, Small Interfering, Umbilical Veins, cytology, Up-Regulation, physiology
Postens nummer:
Posten skapad:
2010-04-30 11:00
Posten ändrad:
2011-01-20 10:00

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