Injury-induced expression of cytokeratins 8 and 18 by vascular smooth muscle cells requires concurrent activation of cytoskeletal and growth factor receptors.
Cytokeratins are not present in the vascular smooth muscle cells (VSMCs) of normal arteries, but they are detectable in the VSMCs of atherosclerotic lesions. A correlation between cytokeratin expression and VSMC phenotype is proposed, but an examination of VSMCs after mechanical injury has yet to be performed. Immunohistochemistry was used to monitor proteins in arterial sections. Western blotting enabled quantification of protein levels. Angioplasty of porcine femoral artery in vivo and porcine coronary artery in vitro served as models of vascular injury. Cytokeratins 8 and 18 were expressed by VSMCs in porcine femoral artery lesions 14 days after balloon angioplasty. Cytokeratins were also present in the neointima of porcine coronary artery segments placed into organ culture for 4 days. Cytokeratin expression was decreased in the presence of inhibitors that affect MAP kinase, PI3 kinase, Src kinase, and G protein, but not in the presence of an AT1 receptor antagonist. Cytokeratin expression also occurred when VSMCs were plated onto collagen in the presence of serum. We conclude that mechanical injury induces expression of cytokeratin 8 and 18 both in vitro and in vivo by synthetic VSMCs that migrate into the neointima. Furthermore, cytokeratin expression requires cellular attachment to extracellular matrix proteins in conjunction with mitogenic stimulation.
Moon
Michael C
MC
University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Yau
Lorraine
L
Wright
Brenda
B
Zahradka
Peter
P
D000800:Angioplasty, Balloon / Q000009:adverse effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005263:Femoral Artery / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000378:metabolism*; D053533:Keratin-8 / Q000378:metabolism*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017534:Radial Artery / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D003598:Cytoskeletal Proteins; C488421:KRT18 protein, human; C426203:KRT8 protein, human; D053538:Keratin-18; D053533:Keratin-8; D047428:Protein Kinase Inhibitors; D017978:Receptors, Growth Factor; D003094:Collagen