Effects of heparinoids on bovine aortic smooth muscle cells
type: CreativeWork
description: Smooth muscle cells (SMCs) comprise the bulk of the tunica media of all blood vessels. Upon injury to the overlying endothelial monolayer of blood vessels, SMCs proliferate into the lumen of the vessel and cause dangerous occlusions. The glycosaminoglycan (GAG) heparin has been shown to be antiproliferative towards SMCs both in vitro and in vivo. The precise molecular mechanism whereby heparin exerts this antiproliferative effect is unknown. The effect of various lengths of heparin treatment on endogenous proteoglycan metabolism in both log and confluent cells was examined. The majority of GAG produced by SMCs is chondroitin sulfate (CS) or dermatan sulfate (DS). Most (90%) of the GAG produced by SMCs is secreted to the culture media. Heparin treatment caused a decrease in the amount of proteoglycans produced, and secreted to the culture media by log cells, while a stimulation of proteoglycan synthesis was observed in confluent cells. Heparin treatment had little effect on the overall type or distribution of proteoglycans in either log or confluent SMCs. Heparin treatment also had little effect on the synthesis of DNA, RNA, or protein by SMCs. The binding and uptake of heparin into SMCs was examined in both log and confluent cells. It was found that log cells exhibit a K$\sb{\rm d}$ of 171 nM for heparin and have 1.5 $\times$ 10$\sp5$ binding sites/cell for heparin. Confluent SMCs have a K$\sb{\rm d}$ of 263 nM for heparin and have 7.9 $\times$ 10$\sp5$ binding sites/cell for heparin. Pre-treatment of cells with heparin prior to binding experiments showed a marked change in both receptor affinity and number of binding sites in log cells. Confluent cells exhibited a decrease in the number of binding sites/cell, but no change in receptor affinity. The binding of heparin to SMCs was examined further through the use of heparin analogs to compete with heparin binding. Heparin was depolymerized by either HONO degradation or periodate oxidation, and these fragments were sc…
abstract: Smooth muscle cells (SMCs) comprise the bulk of the tunica media of all blood vessels. Upon injury to the overlying endothelial monolayer of blood vessels, SMCs proliferate into the lumen of the vessel and cause dangerous occlusions. The glycosaminoglycan (GAG) heparin has been shown to be antiproliferative towards SMCs both in vitro and in vivo. The precise molecular mechanism whereby heparin exerts this antiproliferative effect is unknown. The effect of various lengths of heparin treatment on endogenous proteoglycan metabolism in both log and confluent cells was examined. The majority of GAG produced by SMCs is chondroitin sulfate (CS) or dermatan sulfate (DS). Most (90%) of the GAG produced by SMCs is secreted to the culture media. Heparin treatment caused a decrease in the amount of proteoglycans produced, and secreted to the culture media by log cells, while a stimulation of proteoglycan synthesis was observed in confluent cells. Heparin treatment had little effect on the overall type or distribution of proteoglycans in either log or confluent SMCs. Heparin treatment also had little effect on the synthesis of DNA, RNA, or protein by SMCs. The binding and uptake of heparin into SMCs was examined in both log and confluent cells. It was found that log cells exhibit a K$\sb{\rm d}$ of 171 nM for heparin and have 1.5 $\times$ 10$\sp5$ binding sites/cell for heparin. Confluent SMCs have a K$\sb{\rm d}$ of 263 nM for heparin and have 7.9 $\times$ 10$\sp5$ binding sites/cell for heparin. Pre-treatment of cells with heparin prior to binding experiments showed a marked change in both receptor affinity and number of binding sites in log cells. Confluent cells exhibited a decrease in the number of binding sites/cell, but no change in receptor affinity. The binding of heparin to SMCs was examined further through the use of heparin analogs to compete with heparin binding. Heparin was depolymerized by either HONO degradation or periodate oxidation, and these fragments were sc…
author: Asa, Darwin J.
language: eng
keywords: Chemistry, Biochemistry
date published: 2011-05-07T13:41:40Z
date modified: 2026-07-22T22:25:20Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/22495