       Document 0296
 DOCN  M9610296
 TI    Expression of extracellular matrix genes in adult human dermal
       microvascular endothelial cells and their regulation by heparin and
       endothelial cell mitogens.
 DT    9601
 AU    Hitraya EG; Tan EM; Rudnicka L; Jimenez SA; Department of Medicine,
       Jefferson Medical College, Thomas; Jefferson University, Philadelphia,
       Pennsylvania, USA.
 SO    Lab Invest. 1995 Sep;73(3):393-402. Unique Identifier : AIDSLINE
       MED/96002446
 AB    BACKGROUND: Microvascular alterations are prominent features of systemic
       sclerosis (SSc) and often precede the appearance of clinically
       detectable fibrosis. The mechanism leading to selective microvascular
       injury in SSc is not known; however, microvascular endothelial cell (EC)
       activation has been demonstrated in SSc skin and is considered to be an
       early event in the pathogenesis of SSc. EXPERIMENTAL DESIGN: The
       expression of genes encoding extracellular matrix (ECM) proteins was
       examined in adult human dermal microvascular EC (HDMVEC), human iliac
       vein EC (HIVEC), and human umbilical vein EC (HUVEC) using indirect
       immunofluorescence (IIF) and Northern hybridization analysis. The
       effects of heparin and the endothelial cell mitogens, endothelial cell
       growth factor (ECGF) supplement and acidic and basic fibroblast growth
       factors (aFGF and bFGF), on the expression of ECM genes by these cells
       were also studied. RESULTS: Abundant transcripts for collagen types I,
       IV, VI, and fibronectin (FN) and weak expression of the type III
       collagen gene were detected in HDMVEC cultures in the absence of ECGF
       and heparin. In contrast, in the presence of these factors, no mRNA for
       types I, III, and VI collagens and marked down-regulation (more than
       twofold) of mRNA levels for collagen type IV and FN were observed. These
       results were confirmed at the protein level by IIF staining. In contrast
       to HDMVEC, HIVEC and HUVEC did not show expression of genes encoding
       types I, III, and VI collagens under any culture conditions examined.
       Next we studied the separate effect of heparin and aFGF or bFGF on the
       expression of ECM genes in HDMVEC. In contrast to the maximal expression
       of types I and VI collagens and FN detected in the absence of growth
       factors, aFGF decreased mRNA levels by 43% for type I collagen, by 52%
       for type VI collagen, and by 47% for FN. The decreases in mRNA levels
       caused by bFGF were 37, 41, and 36%, respectively. Heparin alone
       decreased the mRNA levels for these genes by 60, 77, and 65%,
       respectively; however, FGF potentiated the negative effect of heparin on
       ECM gene expression. CONCLUSIONS: These results demonstrate that HDMVEC
       display a unique pattern of expression of ECM genes that is different
       from that displayed by EC from medium and large vessels. The data also
       demonstrate that heparin, ECGF supplement, aFGF, and bFGF regulate ECM
       gene expression in HDMVEC in vitro and suggest that these growth factors
       may modulate the expression of matrix genes in vivo. Altered expression
       of ECM genes by HDMVEC may play an important role in diseases affecting
       the microvasculature, such as SSc.
 DE    Adult  Blotting, Northern  Cells, Cultured  Endothelial Growth
       Factors/*PHARMACOLOGY  Endothelium, Vascular/CYTOLOGY  Extracellular
       Matrix Proteins/*DRUG EFFECTS/*GENETICS  Fibroblast Growth Factor,
       Acidic/PHARMACOLOGY  Fibroblast Growth Factor, Basic/PHARMACOLOGY
       Fluorescent Antibody Technique  Gene Expression Regulation/GENETICS
       Heparin/*PHARMACOLOGY  Human  Iliac Vein/CYTOLOGY
       Microcirculation/*CHEMISTRY  Skin/BLOOD SUPPLY  Support, U.S. Gov't,
       P.H.S.  Umbilical Veins/CYTOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

