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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 1
pubmed:dateCreated
1996-12-20
pubmed:abstractText
Heparin preparations vary in chemical content and in antiproliferative activity for pulmonary artery smooth muscle cells (PASMC). Intracellular alkalinization via stimulation of the Na+/H+ antiporter appears to be a permissive event for proliferation of PASMC. We wondered whether the variable effect of heparin preparations on PASMC growth might be due to different degrees of inhibition of the Na+/H+ antiporter and whether variations in chemical formulation might correlate with the inhibition. Fluorescent microscopy of bovine PASMC was done using a dye with which fluorescence varies directly with intracellular pH (pHi). Bovine PASMC were preincubated with three heparin preparations previously shown to vary in antiproliferative activity, at 1.0 microgram/ml for 24 h. Platelet-derived growth factor (PDGF; 60 ng/ml) on PASMC without heparin resulted in a rise in pHi of 0.27 +/- 0.02 pH units. The rise in pH units in heparin-treated PASMC was 0.34 +/- 0.03 with Choay, 0.21 +/- 0.02 with Elkins-Sinn, and 0.07 +/- 0.02 with Upjohn (+/-SE; all P < 0.05; n = 5). Upjohn heparin incubation for as little as 15 min still impeded the rise in pH induced by PDGF. Heparin did not block the Na+/H+ exchanger directly, as it still restored pHi in response to an acid load. Compared with PASMC proliferation induced by 60 ng/ml PDGF, 1 microgram/ml of Choay, Elkins-Sinn, and Upjohn heparin produced -4 +/- 7.4, 1.4 +/- 4.8, and 48 +/- 2.2% inhibition of PDGF control, respectively (P < 0.05 for Upjohn compared with PDGF and Choay). The heparins varied in protein content and amino acid composition. However, amino acid and glucosamine composition, total sulfation, and extent of 3-O-sulfation did not predict their activity. Thus inhibition of PDGF activation of the Na+/H+ antiporter by a given heparin preparation correlated well with its ability to inhibit PASMC proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L260-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Differential effect of three commercial heparins on Na+/H+ exchange and growth of PASMC.
pubmed:affiliation
Department of Medicine, Massachusetts General Hospital, Boston, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.