The American journal of pathology, 2005-08, Vol.167 (2), p.609-618
2005
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- Autor(en) / Beteiligte
- Titel
- Endothelial KLF2 Links Local Arterial Shear Stress Levels to the Expression of Vascular Tone-Regulating Genes
- Ist Teil von
- The American journal of pathology, 2005-08, Vol.167 (2), p.609-618
- Ort / Verlag
- Bethesda, MD: Elsevier Inc
- Erscheinungsjahr
- 2005
- Quelle
- ScienceDirect
- Beschreibungen/Notizen
- Lung Krüppel-like factor (LKLF/ KLF2 ) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro . We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than ∼5 dyne/cm 2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase ( P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0002-9440eISSN: 1525-2191DOI: 10.1016/S0002-9440(10)63002-7Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1603569
- Format
- –
- Schlagworte
- Adrenomedullin, Animals, Apolipoproteins E - genetics, Apolipoproteins E - physiology, Biological and medical sciences, Blood Vessels - metabolism, Blood Vessels - pathology, Carotid Arteries - metabolism, Cells, Cultured, Endothelin-1 - antagonists & inhibitors, Endothelin-1 - metabolism, Endothelium, Vascular - cytology, Endothelium, Vascular - metabolism, Gene Expression Regulation, Humans, In Situ Hybridization, Investigative techniques, diagnostic techniques (general aspects), Kruppel-Like Transcription Factors, Lasers, Male, Medical sciences, Mice, Mice, Knockout, Nitric Oxide Synthase - antagonists & inhibitors, Nitric Oxide Synthase - metabolism, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Original Research Paper, Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques, Peptides - antagonists & inhibitors, Peptides - metabolism, Pulsatile Flow, RNA, Small Interfering - pharmacology, Stress, Mechanical, Trans-Activators - metabolism