- Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of signaling proteins, primarily known for its role in angiogenesis and vasculogenesis.
- Originally identified in the placenta, PlGF is now recognized as a crucial regulator of blood vessel formation in both physiological and pathological contexts.
- It is a glycoprotein encoded by the PGF gene and exists in several isoforms generated through alternative splicing, with PlGF-1 and PlGF-2 being the most extensively studied. While VEGF-A is indispensable for embryonic vascular development, PlGF is considered non-essential for normal development but becomes particularly important in situations of vascular stress or disease.
- PlGF exerts its biological activity mainly through binding to vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1) and neuropilin co-receptors. By competing with VEGF-A for VEGFR-1 binding, PlGF can indirectly enhance VEGF-A activity on VEGFR-2, which is the primary receptor responsible for angiogenic signaling. In addition, PlGF directly stimulates endothelial cell proliferation, migration, and survival, as well as the recruitment of bone marrow–derived progenitor cells. These functions make PlGF a critical modulator of adaptive angiogenesis in tissues undergoing repair, inflammation, or hypoxia.
- Physiologically, PlGF plays a vital role in placental development during pregnancy by supporting trophoblast growth, differentiation, and vascular remodeling, ensuring adequate maternal–fetal exchange. Dysregulation of PlGF expression is associated with pregnancy-related disorders such as preeclampsia, intrauterine growth restriction, and gestational hypertension. Clinically, circulating levels of PlGF are now used as a biomarker for the early prediction and diagnosis of preeclampsia, with reduced maternal serum PlGF correlating strongly with disease severity and poor pregnancy outcomes.
- Beyond reproduction, PlGF has important implications in cardiovascular disease, cancer, and chronic inflammatory disorders. Elevated PlGF levels have been linked to tumor angiogenesis and metastasis, making it a potential therapeutic target in oncology. Similarly, its upregulation during ischemic cardiovascular disease promotes neovascularization, which can be beneficial for restoring blood flow in damaged tissues. However, in conditions such as atherosclerosis and rheumatoid arthritis, PlGF-driven angiogenesis may exacerbate inflammation and disease progression.
- Because of this dual role, PlGF is being actively investigated both as a diagnostic biomarker and a therapeutic target. Inhibiting PlGF signaling has shown promise in preclinical cancer and inflammatory disease models, while strategies to enhance PlGF activity may aid tissue regeneration after ischemia or injury. Thus, PlGF represents a multifaceted growth factor at the crossroads of developmental biology, vascular physiology, and clinical medicine, with expanding relevance for diagnostics and therapeutics.
