Elevated Basic Fibroblast Growth Factor Levels

Elevated Basic Fibroblast Growth Factor LevelsPulmonary arterial hypertension (PAH) is a devastating illness characterized by a pulmonary vasculopathy that gives rise to an elevation in pulmonary vascular resistance. There has been considerable debate regarding the mechanisms underlying the development of PAH. Although initially focused on vasoconstriction and factors modulating vasomotor tone in the pulmonary circulation, it has more recently been proposed that cellular proliferation of endothelial and smooth-muscle cells is a more central component of the histopathologic changes seen in this disease. The search for molecular pathways that are involved in this cellular proliferation is therefore of particular interest.

Principles of angiogenesis have found application in a wide variety of disease states in clinical medicine. Vascular cellular proliferation is a key component of this process. Histologic evidence suggests that endothelial cell and smooth-muscle cell proliferation is present in the narrowed pulmonary vasculature affected in PAH, and this cellular proliferation is believed to contribute to the development and progression of this disease. Severe endothelial cell proliferation leading to obstruction of the pulmonary vascular bed without significant medial hypertrophy has also been described in PAH. Angiogenic growth factors may have a role in the mechanisms leading to the proliferation of these cells. The plexiform lesions, thin-walled vascular structures distal to sites of vascular obstruction, consisting largely of endothelial cells that express angiogenesis-related molecules, may represent a localized form of pathologic angio-genesis.
Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and permeability factor. VEGF binds to at least two receptors, Flt-1 and Flk-1, expressed by endothelial cells. Flt-1 is associated with cell differentiation, whereas Flk-1 is thought to have a role in VEGF-mediated endothelial cell proliferation. Basic fibroblast growth factor (bFGF), stored in the extracellular matrix, has been documented to have a role in vascular cell migration, endothelial and smooth-muscle cell growth, and synthesis of extracellular matrix proteins. In view of their proliferative effects, these growth factors may have a pathophysiologic role in PAH. As both endothelial cell and smooth-muscle cell proliferation are present in PAH, bFGF may have a particular role because of its effects on both endothelial and smooth-muscle cells.

This entry was posted in Hypertension and tagged angiogenesis, growth substances, pulmonary heart disease.