Different migratory and proliferative properties of smooth muscle cells of coronary and femoral artery.
In the human coronary arteries, the intima begins to thicken from early adolescence and shows progressive thickening with age. We compared the response to vascular injury of the coronary and femoral arteries using a canine model. Both incorporation of 5-bromo-2'-deoxyuridine (BrdU) and neointimal formation after balloon injury were significantly greater in the coronary artery than in the femoral artery. Also, the proliferative and migratory activities of coronary smooth muscle cells (SMCs) were significantly greater than those of femoral SMCs in vitro. The level of phosphorylated myosin light chain (phospho-MLC) was higher in coronary SMCs than in femoral SMCs. Y-27632, a specific inhibitor of Rho-kinase, significantly inhibited the PDGF-induced migration of both coronary and femoral SMCs. In contrast, the migration of coronary SMCs, but not femoral SMCs, was inhibited by ML-9, a specific inhibitor of myosin light chain kinase (MLCK). These findings suggest that the contribution of Rho-kinase and MLCK differs between the different arteries. They also suggest that a neointima develops more easily in the coronary artery than in the femoral artery because of the greater proliferative and migratory activity of coronary SMCs. Differential activation of MLC might partly explain the increased proliferation and migration of coronary SMCs.
Nishiguchi
Futoshi
F
First Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki-city, Osaka 569-8686, Japan. naoko-index@venus.sannet.ne.jp
Fukui
Ryosuke
R
Hoshiga
Masaaki
M
Negoro
Nobuyuki
N
Ii
Masaaki
M
Nakakohji
Takahiro
T
Kohbayashi
Eiko
E
Ishihara
Tadashi
T
Hanafusa
Toshiaki
T
D000577:Amides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D000077214:Becaplermin; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002784:Cholesterol / Q000008:administration & dosage; D003331:Coronary Vessels / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000187:drug effects; D009218:Myosins / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013223:Statistics as Topic; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D054460:rho-Associated Kinases
D000577:Amides; D000925:Anticoagulants; D000963:Antimetabolites; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; C108830:Y 27632; D000077214:Becaplermin; D002784:Cholesterol; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D001973:Bromodeoxyuridine