GROWTH-FACTORS RELEASED INTO THE CORONARY CIRCULATION AFTER VASCULAR INJURY PROMOTE PROLIFERATION OF HUMAN VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE

Objectives. This study sought to 1) assess in vivo release of platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF ) into the coronary circulation after vascular injury in human subject s; and 2) evaluate mitogenic effects of PDGF and bFGF on the patient's own vascular smooth muscle cells (VSMCs). Background. Circumstantial evidence suggests involvement of PDGF and bFGF peptides in the neointi mal response to vascular injury. To date, no study has shown biologica lly active growth factors within the coronary circulation after vascul ar injury in human subjects. Methods. In 18 patients, plasma PDGF AB, platelet factor 4 (PF4) and beta thromboglobulin (beta-TG) levels were measured in coronary sinus blood obtained before and up to 30 min aft er angioplasty. In five patients undergoing atherectomy, coronary sinu s serum was added to cultured VSMCs derived from atherectomy tissue to assess the mitogenic potential of the serum. Mitogenicity attributabl e to PDGF and bFGF was determined using neutralizing antibodies to the se factors. PDGF A, PDGF B and bFGF were localized within the atherect omy tissue using immunocytochemical analysis. Results. Before angiopla sty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patien ts scheduled for angioplasty compared,vith those in control patients ( p < 0.01). Within 5 min of angioplasty, PDGF AB levels increased twofo ld and returned toward preangioplasty levels at 30 min; PF4 and beta-T G levels remained elevated. Serum obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity compared with preatherectom y serum (p = 0.01). This increase in mitogenicity was reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF, bFGF a nd PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized within the intima of the atherectomy tissue. Conclusions. The change i n plasma PDGF level is consistent with first phase release of PDGF aft er vascular injury. The increase in mitogenicity of serum suggests tha t PDGF and bFGF are biologically active. (C) 1997 by the American Coll ege of Cardiology.