Critical Reviews in Oral Biology & Medicine, Vol 6, 230-247, Copyright © 1995 by International & American Associations for Dental Research
The pathophysiology of angiogenesis
P. J. Polverini
Department of Oral Medicine, Pathology, and Surgery, University of Michigan School of Dentistry, Ann Arbor 48109-1078.
The formation of new capillary blood vessels, a process termed
"angiogenesis", is one of the most pervasive and fundamentally essential
biological processes encountered in mammalian organizations. Angiogenesis
is an important event in a variety of physiological settings, such as
embryonic development, chronic inflammation, and wound repair. It is a
process that is tightly regulated in both time and space. Angiogenesis is
driven by a cocktail of growth factors and pro-angiogenic cytokines and is
tempered by an equally diverse group of inhibitors of neovascularization.
Angiogenesis is also central to the etiology and pathogenesis of a number
of pathological processes that include, among others, solid tumors,
diseases of the eye, and chronic inflammatory disorders such as rheumatoid
arthritis, psoriasis, and periodontitis. Based on recent work from several
laboratories, it is now eminently clear that most if not all angiogenesis
and vasoproliferative-dependent disease processes are not only a
consequence of the unrestricted production of normal or aberrant forms of
pro-angiogenic mediators but also the result of a relative deficiency in
angiogenic-inhibitory molecules. In this review, I will describe how these
multifunctional mediator systems function to coordinate and regulate the
angiogenic response, and how disruption in the molecular controls that
regulate the production of pro-angiogenic and angiostatic mediators leads
to aberrant angiogenesis and disease. The implications of these findings in
the development of novel therapeutic strategies for the treatment of
diseases characterized by disregulated angiogenesis will also be discussed.
