title: Identification of mechanically induced genes in human monocytic cells by DNA microarrays.
abstract: BACKGROUND
  Hypertension is a risk factor for coronary heart disease. Macrophages are critically involved in both atherogenesis and plaque instability. Although macrophages may be subjected to excess mechanical stress in these diseases, the way in which biomechanical forces affect macrophage function remains incompletely defined.
  
  
  OBJECTIVE
  To investigate the molecular response to mechanical force in macrophages.
  
  
  METHODS
  We used a DNA microarray with 1056 genes to describe the transcriptional profile of mechanically induced genes in human monocytic THP-1 cells. Mechanical deformation was applied to a thin and transparent membrane on which cells were cultured. After THP-1 cells were pre-incubated in the presence of phorbol 12-myristate 13-acetate (0.2 micromol/l) for 24 h, THP-1 cells attached to the membrane were subjected to biaxial mechanical strain. Interleukin-8 concentrations were determined using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In DNA microarray analysis, cyclic mechanical strain at 1 Hz induced only three genes more than 2.5-fold at 3 and 6 h in THP-1 cells: prostate apoptosis response-4 (3.0-fold at 3 h, 6.7-fold at 6 h), interleukin-8 (4.3-fold at 6 h) and the immediate-early response gene, IEX-1 (2.6-fold at 6 h). Real-time reverse transcriptase polymerase chain reaction analysis confirmed the amplitude-dependent induction of these three genes. In addition, mechanical strain increased interleukin-8 protein expression.
  
  
  CONCLUSIONS
  The present study demonstrates that human monocytic cells respond to mechanical deformation with induction of immediate-early and inflammatory genes. These findings suggest that mechanical stress in vivo, such as that associated with hypertension, may play an important part in atherogenesis and instability of coronary artery plaques, through biomechanical effects on vascular macrophages.
authors.affiliation: Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Tochigi, Japan.
authors.forename: Ruri
authors.initials: R
authors.lastname: Ohki
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
authors.forename: Uichi
authors.initials: U
authors.lastname: Ikeda
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
mesh_terms: D051017:Apoptosis Regulatory Proteins; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D009000:Monocytes / Q000502:physiology*; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C101296:prostate apoptosis response-4 protein