Circulation, Vol 85, 543-553, Copyright © 1992 by American Heart Association
G Leclerc, JM Isner, M Kearney, M Simons, RD Safian, DS Baim and L Weir
BACKGROUND. Identification of genes that are specifically activated in
restenosis lesions after percutaneous transluminal angioplasty represents a
necessary step toward molecular manipulation designed to inhibit cellular
proliferation responsible for such lesions. Whereas quiescent smooth muscle
cells (contractile phenotype) preferentially express smooth muscle myosin,
proliferating smooth muscle cells (synthetic phenotype) have been shown to
preferentially express nonmuscle myosin in vitro. Accordingly, we analyzed
the expression of a recently cloned isoform of human nonmuscle myosin heavy
chain (MHC-B) in fresh human restenotic lesions. METHODS AND RESULTS. A
total of 10 lesions, including four restenosis (three superficial femoral
arterial lesions and one saphenous vein bypass lesion) and six primary
(four superficial femoral arterial lesions and two coronary arterial
lesions) obtained percutaneously by directional atherectomy, were processed
for examination by in situ hybridization. In total, 150 tissue sections of
restenotic lesions (66 sections), primary lesions (78 sections), and normal
internal mammary artery (six sections) were hybridized with the nonmuscle
MHC-B probe. Restenotic lesions showed intense hybridization to the
nonmuscle MHC-B cRNA probe, as demonstrated by a clustering of more than 20
grains per cell nucleus in 80% of the cells examined within a high-power
field (x250); in contrast, an equivalent degree of hybridization was
observed in only 7% of cells within primary lesions (p less than 0.001).
Results of immunocytochemistry using monoclonal antibody to smooth muscle
actin indicated that cells demonstrating strong hybridization were smooth
muscle in origin. CONCLUSIONS. These findings demonstrate that 1) human
vascular tissue obtained by percutaneous directional atherectomy
constitutes appropriate biopsy material for gene expression studies at the
mRNA level, and 2) nonmuscle MHC-B mRNA is present in greater abundance
among restenotic versus primary vascular stenoses. These observations thus
provide a rational basis to explore restenotic lesions on a larger scale to
identify genes that are activated in these lesions and establish potential
targets for future gene therapy.
ARTICLES
Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy
Department of Medicine (Cardiology Division), St. Elizabeth's Hospital, Tufts University School of Medicine, Boston, Mass.
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