FGF Induces Hypertrophy and Angiogenesis in Hibernating Myocardium
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
See related article, pages 767–775
For several years there has been considerable interest in stimulating angiogenesis by a variety of growth factors, including the family of fibroblast growth factors (FGF). FGF-5 is a protooncogene known to stimulate cell growth and proliferation in multiple cell types, including cancer.1 The cardiac myocyte can also produce different isoforms of FGFs, eg, it has been shown that the expression of basic FGF increases in hibernating myocardium,2 which was the disease state of interest in the current study published in Circulation Research.3 The most commonly cited effect of FGF-5 in the heart is to promote angiogenesis. Several studies have shown that gene transfer of FGF-5 in the heart increases vessel formation and regional blood flow.4–6 This effect is mediated by a production of FGF-5 by the cardiac myocytes, followed by its release in the extracellular space. In addition, FGF-5 can function as an autocrine/paracrine mechanism of cardiac cell growth and as a cytoprotective mechanism against irreversible ischemic damage.7
Indeed, most of the prior interest on the role of FGF has been in the field of angiogenesis, where swine models of chronic ischemia have been shown to increase blood flow, presumably through angiogenesis.4–6,8–10 In contrast, the article by Suzuki et al,3 concluded that gene therapy with FGF improved function in their swine model of hibernating myocardium, but the mechanism of the salutary effect involved “rather than angiogenesis, stimulation of hypertrophy and re-entry of a small number of myocytes into the mitotic phase of the cell cycle… ”3
These observations are conceptually important in that the focus of prior studies on treating chronically ischemic myocardium has been on angiogenesis, and not directed at improving function through …