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Mol Endocrinol 13:705–717. Westphal RS, Tavalin SJ, Lin JW, et al.: 1999. Regulation of NMDA receptors by an asso- ciated phosphatase–kinase signaling com- plex. Science 285:93–96. PII S1050-1738(02)00167-6 TCM Sandro De Falco, Bruno Gigante, and M. Graziella Persico are at the International Institute of Genetics and Biophysics, CNR, Napoli, Italy. * Address correspondence to: M. Graziella Persico, International Institute of Genetics and Biophysics, CNR, Via Pietro Castellino, III, 80131 Napoli, Italy. Tel.: (+39) 081- 6132294; Fax: (+39) 081-6132352; e-mail: persico@iigb.na.cnr.it. © 2002, Elsevier Science Inc. All rights reserved. 1050-1738/02/$-see front matter Structure and Function of Placental Growth Factor Sandro De Falco, Bruna Gigante, and M. Graziella Persico* Placental growth factor (PlGF) belongs to the same family as the vas- cular endothelial growth factor A (VEGF-A). Recent gene inactivation studies in mice have demonstrated that loss of PlGF does not affect development, reproduction, or normal postnatal life. However, the mice show significantly impaired angiogenesis and arteriogenesis during pathological conditions such as ischemia and tumor forma- tion, conditions in which the expression of VEGF-A is normally increased. Mice expressing a truncated form of the specific receptor for PlGF, the VEGF receptor 1 (VEGFR-1), show impaired angiogene- sis similar to that observed in Plgf -/- mice. These data suggest a piv- otal role for PlGF and VEGFR-1 in regulating VEGF-A-dependent angiogenesis under pathological conditions. VEGF-A has been uti- lized for the therapeutic stimulation of new blood vessels in ischemic hearts and limbs, with controversial results from the initial clinical experience. This review discusses the possibility of using the PlGF/ VEGFR-1 pathway as an alternative target for angiogenic therapy. (Trends Cardiovasc Med 2002;12:241–246). © 2002, Elsevier Sci- ence Inc. collateral vessels, also known as adapta- tive arteriogenesis. These two phenom- ena are tightly regulated and are part of physiological processes such as the re- sponse of the heart and skeletal muscles to physical exercise or the modifications in the uterus and the ovary during dif- ferent phases of the menstrual cycle (Moulton and Folkman 1999). Lack of an appropriate vascular response is one of the factors that ultimately leads to cardiac failure in diseases such as hy- pertension and ischemic cardiomyopa- thy, and to a reduced ability to walk in peripheral atherosclerosis. In the last 20 years, the search for the molecular mediators of angiogenesis has identified several genes implicated in the development and maintenance of the car- diovascular system. Among these genes, particular attention has been given to growth factors and their receptors that allow communication between cells of different tissues. Misregulated growth and remodeling of blood vessels has been implicated in a broad spectrum of human disorders in which increased or decreased vascular- ization of target tissues and organs ap- pears to be involved in the pathogenesis of the disease (Table 1; Carmeliet and Jain 2000). In adult life, angiogenesis occurs through two fundamental mechanisms: the growth of new vessels from capillar- ies and the enlargement of pre-existing