Cardiac alpha-actin in smooth muscle cells: detection in umbilical cord vessels and in atherosclerotic lesions.
Phenotypic modulation of smooth muscle cells (SMC) is a key event during the development of atherosclerotic and restenotic lesions. During this process, the composition of the cytoskeleton is substantially altered, with changes predominantly in actin expression reflecting a shift from smooth muscle alpha-actin to the non-muscle beta-isoform. We now demonstrate that yet another actin isoform, cardiac alpha-actin, is synthesized, de novo, in SMC of various atherosclerotic lesions. Using a highly specific monoclonal antibody against cardiac alpha-actin, we analyzed and compared the accumulation of this actin isoform in diverse SMC by immunofluorescence microscopy and immunoblotting. As expected, cardiac alpha-actin was present in human myocardium but not in healthy SMC of adult aorta, coronary arteries, trabeculae of the spleen, colon, stomach or skeletal muscle. Interestingly, the presence of cardiac alpha-actin was detected in umbilical cord vessels, human myometrium, in atherosclerotic coronary lesions and atherosclerotic lesions from peripheral vascular disease. The distribution of cardiac alpha-actin often paralleled that of cytokeratins 8 and 18, intermediate filament proteins typically found in dedifferentiated SMC. Taken together, the data presented here illustrate the expression of cardiac alpha-actin to be limited to either fetal vessels or those vessels or tissue having suffered damage or atrophy, outside its 'native' environment in the heart. The demonstration of cardiac alpha-actin in SMC of umbilical cord vessels and in atherosclerotic lesions but not in apparently healthy vessels supports the notion that SMC in atherosclerotic lesions exhibit a dedifferentiated phenotype.
Bea
F
F
Universitätsklinik Heidelberg, Medizinische Klinik III, Germany.
Bär
H
H
Watson
L
L
Blessing
E
E
Kübler
W
W
Kreuzer
J
J
Jahn
L
L
D000199:Actins / Q000032:analysis*; D001011:Aorta / Q000737:chemistry; D001161:Arteriosclerosis / Q000378:metabolism*; D003331:Coronary Vessels / Q000737:chemistry; D005260:Female; D006801:Humans; D007633:Keratins / Q000032:analysis; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000737:chemistry*; D009206:Myocardium / Q000737:chemistry*; D011247:Pregnancy; D020033:Protein Isoforms / Q000032:analysis; D014471:Umbilical Veins / Q000737:chemistry*
D000199:Actins; D020033:Protein Isoforms; D007633:Keratins