title: Does cellular sex matter? Dimorphic transcriptional differences between female and male endothelial cells.
abstract: OBJECTIVE
  Significant sex differences exist in cardiovascular diseases. Although an impact of gonadal hormones is presumed, it is largely unknown whether sexually dimorphic gene expression also plays a role and whether cells themselves show intrinsic sex differences.
  
  
  METHODS
  We performed whole genome expression analyses in human umbilical vein endothelial cells (HUVEC) from 20 male and 20 female donors and compared levels of gene transcription between the sexes. To further assess whether there is a sex-specific response to stress, we subjected male and female HUVEC to shear for 24 h and analysed changes in gene expression.
  
  
  RESULTS
  Genes indicative for greater immune responsiveness were stronger expressed in female compared to male HUVEC. There was a significant enrichment of 77 immune-related genes in female HUVEC. These increased transcriptional levels in female cells were verified for 20 genes by real-time RT-PCR. 6.7% of all mRNAs were regulated by shear stress. Female HUVEC showed a more pronounced transcriptional response to shear than did their male counterparts. In addition to quantitative differences, a number of genes were regulated in the opposite direction between the two sexes by shear stress. Functionally, female HUVEC showed a higher cell viability after serum starvation and an increased tube formation capacity compared to male cells.
  
  
  CONCLUSIONS
  These findings underscore the importance for differentiation between male and female cells in cell culture experiments. This may apply not only to endothelial cells but might be generalized to other cell types as well. The observed sexual dimorphisms in gene expression in endothelial cells may contribute to sex differences between males and females in endothelial function.
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Lorenz
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Koschate
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kaufmann
authors.affiliation: Miltenyi Biotec GmbH, Bioinformatics, Bergisch Gladbach, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Kreye
authors.affiliation: Institut für Physiologie, CharitéCentrum 2, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Mertens
authors.affiliation: Institut für Physiologie, CharitéCentrum 2, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Baumann
authors.affiliation: Klinik für Frauenheilkunde und Geburtshilfe, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gossing
authors.affiliation: Institut für Physiologie, CharitéCentrum 2, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Alex
authors.initials: A
authors.lastname: Marki
authors.affiliation: Institut für Physiologie, CharitéCentrum 2, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zakrzewicz
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Miéville
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Benn
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Horbelt
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Wratil
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl
authors.affiliation: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany. Electronic address: verena.stangl@charite.de.
authors.forename: Verena
authors.initials: V
authors.lastname: Stangl
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012727:Sex Characteristics; D012737:Sex Factors; D013314:Stress, Mechanical; D013312:Stress, Physiological; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D005819:Genetic Markers
keywords: Endothelial cells; Gender; Gene expression; HUVEC; Sex; Shear stress; Tube formation