SMOOTH-MUSCLE CELL ABUNDANCE AND FIBROBLAST GROWTH-FACTORS IN CORONARY LESIONS OF PATIENTS WITH NONFATAL UNSTABLE ANGINA - A CLUE TO THE MECHANISM OF TRANSFORMATION FROM THE STABLE TO THE UNSTABLE CLINICAL STATE

Background. The mechanisms responsible for the transformation of stabl e angina to unstable angina, a major cause of morbidity and mortality, are commonly believed to be plaque rupture and thrombosis. We determi ned whether additional mechanisms are operative by analyzing the histo pathology and immuno-histopathology of coronary plaques retrieved by d irectional atherectomy of patients with unstable angina in whom no int raluminal thrombus was demonstrated by angiography. Methods and Result s. The histological findings of atherectomy specimens from 34 patients with unstable angina were compared with those of 24 patients with pos tangioplasty restenosis, whose lesions are known to be composed of smo oth muscle cells (SMCs), and 10 patients with stable angina, whose les ions contain relatively few SMCs. We also studied the expression of ac idic and basic fibroblast growth factors (aFGF and bFGF), whose role i n the vascular response to injury has been established. Specimens from unstable angina resembled those from postangioplasty restenosis in re gard to SMC abundance (scale, 0 to 3; 1.4+/-0.9 versus 1.7+/-0.9; P=NS ), and both differed from those of stable angina. Thrombus and/or hemo rrhage occurred in only 34% of patients with unstable angina (compared with 6% of restenosis patients and in none of stable angina patients) . Active lesions (defined as lesions containing one or more of the fol lowing: thrombus, hemorrhage, abundant and disorganized SMCs in the pr esence of loose connective tissue, or inflammatory infiltrate) were ob served in 56% of the unstable angina patients and in 50% of the resten osis patients but in none of the stable angina patients. The expressio n of aFGF and bFGF was detected in 80% to 1004b of unstable angina (n= 11) and restenosis (n=10) specimens but in only 1 of 5 stable angina s pecimens. Conclusions. Microscopic evidence of thrombosis and plaque r upture occurred in only one third of unstable angina patients, selecte d because they had no angiographic evidence of intracoronary thrombus. Moreover, their lesions resembled those of restenosis patients in reg ard to SMC abundance, lesion activity, and the expression of aFGF and bFGF. Our findings therefore suggest that an alternative mechanism to plaque rupture and thrombus formation may be operative in the precipit ation of unstable angina; namely, in a subset of patients, SMC prolife ration may lead to gradual plaque expansion and thereby to lumenal nar rowing and unstable angina. Our data also suggest a role for aFGF and bFGF in this process.