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 v ascular smooth muscle cells and may mediate vasculopathy in cardiac al lografts subjected to chronic immunological injury. Therefore, we exam ined cardiac expression of aFGF, the number of rejection episodes, and other potential risk factors in 32 heart transplant patients who unde rwent intravascular ultrasound (IVUS) for detection of cardiac allogra ft vasculopathy (CAV). As defined by IVUS, CAV was present in 21 patie nts and absent in 11 patients (follow-up time: 52+/-21 vs. 51+/-12 mon ths, respectively, P=NS), The level of aFGF in myocardial biopsies obt ained at the time of IVUS was measured by semiquantitative reverse tra nscriptase polymerase chain reaction and expressed as the aFGF:GAPDH r atio. 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 wi thout CAV [P<0.001]). A strong association was found between high leve ls of cardiac aFGF and CAV, as 18 of 19 patients (95%) with high level s 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 num ber of untreated low grade rejection episodes was 3.5+/-1.8 in patient s with vs. 2.1+/-1.0 in patients without CAV [P=0.04]). Among other ri sk factors examined (age, sex, serum cholesterol, blood pressure, CMV infection, dose of immunosuppressants, and ischemic time), only trigly cerides were higher in patients with than those without CAV (P=0.003). We conclude that increased cardiac production of aFGF is significantl y associated with CAV, which suggests that aFGF may serve as an import ant mediator in CAV. Untreated low grade rejection also poses an incre ased risk for CAV.