Biological Functions of the Low and High Molecular Weight Protein Isoforms of Fibroblast Growth Factor-2 in Cardiovascular Development and Disease

Fibroblast growth factor 2 (FGF2) consists of multiple protein isoforms (low molecular weight, LAM, and high molecular weight, HAW) produced by alternative translation from the Fgt2 gene. These protein isoforms are localized to different cellular compartments, indicating unique biological activity. FGF2 isoforms in the heart have distinct roles in many pathological circumstances in the heart including cardiac hypertrophy, ischemia-reperfusion injury, and atherosclerosis. These studies suggest distinct biological activities of FGF2 LAM and HMW isoforms both in vitro and in vivo. Yet, due to the limitations that only the recombinant FGF2 LMW isoform is readily available and that the FGF2 antibody is nonspecific with regards to its isoforms, much remains to be determined regarding the role(s) of the FGF2 LMW and HMW isoforms in cellular behavior and in cardiovascular development and pathophysiology. This review summarizes the activities of LMW and HMW isoforms of FGF2 in cardiovascular development and disease. Developmental Dynamics 238:249-264, 2009. (c) 2008 Wiley-Liss, Inc.