ASSOCIATION OF ACIDIC FIBROBLAST GROWTH-FACTOR AND UNTREATED LOW-GRADE REJECTION WITH CARDIAC ALLOGRAFT VASCULOPATHY

Acidic fibroblast growth factor (aFGF) is a potent growth factor for vascular smooth muscle cells and may mediate vasculopathy in cardiac allografts subjected to chronic immunological injury. Therefore, we examined cardiac expression of aFGF, the number of rejection episodes, and other potential risk factors in 32 heart transplant patients who underwent intravascular ultrasound (IVUS) for detection of cardiac allograft vasculopathy (CAV). As defined by IVUS, CAV was present in 21 patients and absent in 11 patients (follow-up time: 52+/-21 vs. 51+/-12 months, respectively, P=NS), The level of aFGF in myocardial biopsies obtained at the time of IVUS was measured by semiquantitative reverse transcriptase polymerase chain reaction and expressed as the aFGF:GAPDH ratio. Higher levels of aFGF were associated with CAV (mean aFGF: GAPDH ratio was 1.45+/-0.99 in patients with vs. 0.18+/-0.12 in patients without CAV [P<0.001]). A strong association was found between high levels of cardiac aFGF and CAV, as 18 of 19 patients (95%) with high levels of aFGF (aFGF:GAPDH >1) but only 3 of 13 patients with low levels of aFGF had CAV (P<0.001). The relative risk of high level aFGF for CAV was 4.1. Untreated low grade rejection (ISHLT I), but not treated high grade rejection (ISHLT >2), was also associated with CAV (average number of untreated low grade rejection episodes was 3.5+/-1.8 in patients with vs. 2.1+/-1.0 in patients without CAV [P=0.04]). Among other risk factors examined (age, sex, serum cholesterol, blood pressure, CMV infection, dose of immunosuppressants, and ischemic time), only triglycerides were higher in patients with than those without CAV (P=0.003). We conclude that increased cardiac production of aFGF is significantly associated with CAV, which suggests that aFGF may serve as an important mediator in CAV. Untreated low grade rejection also poses an increased risk for CAV.