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Physiologic cyclic strain stimulates heme oxygenase‐1 gene expression in endothelial cells: role in cell survival and proliferation
Author(s) -
Durante William,
Liu Xiaoming,
Peyton Kelly J.
Publication year - 2013
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.27.1_supplement.1127.4
Subject(s) - heme oxygenase , strain (injury) , apoptosis , heme , chemistry , microbiology and biotechnology , cell growth , signal transduction , gene expression , gene , biology , biochemistry , anatomy , enzyme
Endothelial cells (ECs) are constantly subjected to cyclic strain that arises from the periodic change in vessel wall diameter as a result of pulsatile blood flow. Application of physiologic levels of cyclic strain regulates EC proliferation and apoptosis; however, the underlying mechanisms are not known. Since heme oxygenase‐1 (HO‐1) is a potent modulator of EC function, the present study investigated whether HO‐1 contributes to the biological actions of cyclic strain. Administration of physiologic cyclic strain (6% at 1 hertz) to human aortic ECs stimulated an increase in HO‐1 mRNA, protein, and activity that was prevented by the antioxidant N‐acetyl‐ L‐cysteine. Cyclic strain also evoked an increase in HO‐1 promoter activity that was blocked by mutating the antioxidant response element in the promoter or by overexpressing dominant‐negative Nrf2. Finally, application of cyclic strain inhibited EC apoptosis and proliferation. Although pharmacological inhibition or genetic deletion of HO‐1 reversed the anti‐apoptotic effect, it enhanced the anti‐proliferative action of cyclic strain. In conclusion, the present study demonstrates that physiologic cyclic strain stimulates HO‐1 gene expression via an oxidative pathway that involves Nrf2, and that induction of HO‐1 promotes the anti‐apoptotic action of cyclic strain while counteracting its anti‐proliferative effect. Supported by NIH grant HL59976.