The discovery of placenta growth factor and its biological activity

Abstract

Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.

Figure 1

Schematic representation of binding properties of PlGF isoforms and PlGF/VEGF heterodimer. The possible dimers formed by PlGF monomer (gray) are represented. In the case of PlGF isoforms 2 and 4, the heparin-binding domain is represented by additional filled oval. For the heterodimer, the VEGF moiety is in orange. For VEGF receptors (green VEGFR-1, yellow VEGFR-2) the seven Ig-like domains are represented as half ovals, whereas filled rectangles represent the intracellular TK domains. The extracellular Neuropilins receptor 1 and 2 domains are represented as vertical ovals (domains ai, a2), square (b1, b2) and an horizontal oval (domain c) (Mamluk et al., 2002). Heparan sulfate is represented in red.