Reinjury of Arterial Lesions Induces Intimal Smooth Muscle Cell Replication That Is Not Controlled by Fibroblast Growth Factor 2

• Published in: Circulation research 1997-03, Vol.80 (3), p.408-417
• Main Authors: Koyama, Hiroyuki, Reidy, Michael A
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Angioplasty - adverse effects; Animals; Biological and medical sciences; Blood vessels and receptors; Blotting, Western; Carotid Arteries - drug effects; Carotid Arteries - pathology; Carotid Arteries - physiopathology; Cell Count; Cell Division - drug effects; Cell Division - physiology; Fibroblast Growth Factor 2 - pharmacology; Fibroblast Growth Factor 2 - physiology; Fundamental and applied biological sciences. Psychology; Heparin - pharmacology; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - physiopathology; Rats; Rats, Sprague-Dawley; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Fibroblast Growth Factor - metabolism; Recombinant Proteins; Time Factors; Tunica Intima - drug effects; Tunica Intima - injuries; Tunica Intima - pathology; Tunica Intima - physiopathology; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.0000435857.23307.bd

In this study we have examined the response of rat carotid arteries with intimal lesions to an angioplasty injury. Rat carotid arteries were subjected to injury with a 2F Fogarty catheter (first injury), and 28 days later the same arteries were subjected to reinjury with a 1.5-mm-diameter coronary dilation catheter (second injury) or a sham operation. After the second injury, the injured arterial surfaces were covered by a platelet monolayer, with occasional small thrombi. The size of the intimal area was significantly increased 28 days after the second injury, although the luminal area was not changed at this time. Intimal and medial cell replication, measured by 5-bromo-2 prime-deoxyuridine labeling, was significantly increased at 2 days after the second injury but was markedly reduced by 7 days. Addition of fibroblast growth factor-2 (FGF2, 60 micro g IV) did not increase smooth muscle cell (SMC) replication in arteries subjected to the second injury, and replication was not inhibited with an antibody against FGF2 (120 mg IV). Both these reagents, however, did significantly affect SMC replication in normal carotid arteries subjected to Fogarty catheter injury. In a similar manner, heparin (888 UPS units/kg body wt IV) did not inhibit cell replication after second injury, although it did suppress SMC replication after a single injury. One conclusion is that rat intimal cells in vivo are different from medial SMCs and that other, as-yet-unknown, factors are important for their proliferation. (Circ Res. 1997;80:408-417.)