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Impact of substrate stiffness and hypoxia on endothelial spreading and contratility
Author(s) -
Kuhr Frank K,
Schraufnagle Dean E.,
Christman John W,
Yuan Jason X.-J.,
Levitan Irena
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.841.3
Subject(s) - angiogenesis , contractility , hypoxia (environmental) , microbiology and biotechnology , endothelial stem cell , chemistry , lung , contraction (grammar) , biology , medicine , endocrinology , in vitro , biochemistry , organic chemistry , oxygen
Hypoxia is known to promote proliferation of endothelial cells (ECs) and facilitate angiogenesis to restore a functional vasculature. However, conditions such as pulmonary fibrosis and scleroderma that result in an increase in tissue stiffness may impair endothelial function and inhibit angiogenesis. Little, however, is known about the sensitivity of lung microvascular endothelial cells to substrate stiffness. Here we show that in contrast to aortic endothelial cells that spread more on stiff substrates, human microvascular endothelial cells from the lung (HMVEC‐L) spread more and proliferate better on softer versus stiffer substrates (0.5 mg/ml compared to 1.5mg/ml type I collagen) in three‐dimensional collagen gels. We also show that HMVEC‐L contractility, the ability of the cells to generate force, in both soft and stiff gels was significantly facilitated by hypoxic conditions (3% O 2 ), as evidenced by gel‐contraction assays. The contractile phenotype is not due to an increase in proliferation as the cell number in both hypoxic and normoxic conditions were similar after 48 hrs. We propose that hypoxia‐induced increase in endothelial contractility contributes to the angiogenic response to hypoxic conditions but that it might be compromised by an increase in tissue stiffness. Supported by T32 HL 82547‐5, HL083298,