- Placental growth factor-1 (PlGF-1) is one of the major isoforms of placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family that plays a central role in angiogenesis, vasculogenesis, and tissue remodeling.
- PlGF-1 is produced through alternative splicing of the PGF gene and is characterized as a soluble, diffusible isoform lacking the heparin-binding domain found in PlGF-2. This structural distinction gives PlGF-1 unique biological properties, particularly in terms of receptor binding and bioavailability in the extracellular environment.
- Functionally, PlGF-1 exerts its activity mainly through binding to vascular endothelial growth factor receptor-1 (VEGFR-1, also called Flt-1) and its soluble decoy form (sFlt-1). By competing with VEGF-A for VEGFR-1 binding, PlGF-1 can regulate the distribution of VEGF-A between VEGFR-1 and VEGFR-2, indirectly modulating angiogenic signaling. PlGF-1 also recruits monocytes and other bone marrow–derived progenitor cells to sites of ischemia or injury, contributing to tissue repair and vascular remodeling. Unlike VEGF-A, which is indispensable for embryonic vascular development, PlGF-1 is dispensable under normal physiological conditions but becomes particularly important in pathological or stress contexts, such as ischemia, inflammation, wound healing, and tumor growth.
- In pregnancy, PlGF-1 contributes to the proper vascularization of the placenta, ensuring adequate maternal–fetal exchange of nutrients and oxygen. Altered expression of PlGF-1, alongside other PlGF isoforms, has been linked to pregnancy complications. Low maternal circulating PlGF-1 (and total PlGF) is strongly associated with preeclampsia, intrauterine growth restriction (IUGR), and other forms of placental dysfunction. Because of this, PlGF (including PlGF-1) has become a clinically important biomarker for early prediction, diagnosis, and risk stratification of preeclampsia.
- Beyond reproduction, PlGF-1 has been implicated in several pathological processes. In cardiovascular disease, its upregulation during ischemia promotes collateral vessel growth and neovascularization, aiding tissue survival. However, in chronic inflammatory diseases and cancer, sustained PlGF-1 activity may worsen pathology by fueling angiogenesis, inflammation, and immune cell recruitment. Tumors, in particular, often exploit PlGF-1 to create a supportive microenvironment for growth and metastasis. These dual effects—protective in ischemia but potentially harmful in cancer and chronic inflammation—highlight the complex, context-dependent roles of PlGF-1.
- Therapeutically, both inhibition and enhancement of PlGF-1 signaling have been explored. Neutralizing antibodies against PlGF have been investigated for their potential to block pathological angiogenesis in cancer and ocular diseases. Conversely, PlGF-1 administration or gene therapy approaches have been studied to enhance vascular growth and repair in ischemic cardiovascular disease. The therapeutic balance lies in selectively harnessing its angiogenic and tissue-repairing effects while avoiding pathological overactivation.
