Accelerated nonmuscle contraction after subarachnoid hemorrhage: culture and characterization of myofibroblasts from human cerebral arteries in vasospasm.
Cell culture lines from human cerebral arteries showing vasospasm after subarachnoid hemorrhage were established from three autopsy cases. Each culture line showed the ultrastructural characteristics of myofibroblasts. Decreased alpha-actin antigenicity, demonstrated using the anti-smooth muscle cell alpha-actin antibody, was observed in cultured cells possessing abundant F-actin. When incorporated into the three-dimensional collagen matrix in vitro, the cultured cells compacted the collagen lattice at a rate equivalent to that of human dermal fibroblasts. Lattice compaction was significantly accelerated by cerebrospinal fluid taken from patients with symptomatic vasospasm. Compaction was completely inhibited by the addition of 10(-6) mol/L verapamil or 100 U/mL heparin. Neither nimodipine (10(-5) mol/L) nor nicardipine (10(-5) mol/L) inhibited compaction, and endothelin (10(-6) mol/L) and potassium chloride (40 mmol/L) had no effect. The morphological change of cells in the collagen lattice suggests that both verapamil and heparin affect cellular motility, filopodial protrusion, and cell attachment. These data suggest that myofibroblasts in human cerebral arteries differ from medial smooth muscle cells and can generate a force rearranging the proliferated collagen matrix present after subarachnoid hemorrhage. This reorganization can contribute to, or be responsible for, sustained vasoconstriction. Consequently, current treatment for vasospasm may need to be reevaluated to include the nonmuscle components in the vessel wall.
Yamamoto
Y
Y
Department of Neurosurgery, University of Mississippi Medical Center, Jackson.
Smith
R R
RR
Bernanke
D H
DH
D000368:Aged; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects / Q000473:pathology*; D003094:Collagen / Q000648:ultrastructure; D003285:Contractile Proteins / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000134:cerebrospinal fluid / Q000209:etiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011189:Potassium Chloride / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications
D002121:Calcium Channel Blockers; D003285:Contractile Proteins; D016232:Endothelins; D011189:Potassium Chloride; D006493:Heparin; D003094:Collagen