KINETICS OF CELLULAR PROLIFERATION AFTER ARTERIAL INJURY .2. INHIBITION OF SMOOTH-MUSCLE GROWTH BY HEPARIN

  • 1 January 1985
    • journal article
    • research article
    • Vol. 52  (6) , 611-616
Abstract
Heparin inhibits intimal thickening after arterial injury. Whether this effect is due to inhibition of medial smooth muscle cell (SMC) migration, SMC proliferation in the intima, or synthesis and deposition of connective tissue has not been evident. These possibilities were investigated in a rat carotid balloon injury model. Heparin (0.3 mg/kg per h) was administered i.v. by means of osmotic pumps to experimental animals, and controls received lactated Ringer''s solution. Smooth muscle proliferation (thymidine index), intimal smooth muscle accumulation, and endothelial regeneration were measured at intervals between 0-28 days. Total smooth muscle growth, as determined biochemically at 14 days, was markedly inhibited by heparin if the pumps were placed 24 h before or at the time of injury, and less so if inserted 48 or 96 h after injury. SMC thymidine indices were maximal in the media at 4 days and in the intima at 7 days for injured arteries of both heparin-treated and control rats; at each time point, SMC proliferation and intimal thickening were less in heparin-treated rats. The volume of connective tissue in the intima was the same in both groups at 28 days. Medial SMC migration into the intima was diminished by heparin treatment, but endothelial regreneration was not affected. Apparently, heparin is a specific inhibitor of SMC migration and proliferation, and is most effective if started before SMC enter S-phase.