Abstract
Placental Growth Factor (PGF) is a key molecule in angiogenesis. Several studies have revealed an important role of PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation, cardiovascular diseases and inflammatory processes) suggesting its use as a potential therapeutic agent. However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors: a study sample from two isolated villages in the Cilento region, South Italy (N = 871) and a replication sample from the general Danish population (N = 1,812). A significant difference in PGF mean levels was found between the two cohorts. However, in both samples, we observed a strong correlation of PGF levels with ageing and sex, men displaying PGF levels significantly higher than women. Interestingly, smoking was also found to influence the trait in the two populations, although differently. We have then focused on genetic risk factors. The association between five single nucleotide polymorphisms (SNPs) located in the PGF gene and the plasma levels of the protein was investigated. Two polymorphisms (rs11850328 and rs2268614) were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability.
Highlights
Placental growth factor (PGF), originally identified in the placenta, is a protein highly homologous to vascular endothelial growth factor (VEGF) [1]
A significant increase in Placental Growth Factor (PGF) plasma levels with ageing was detected in the Cilento sample (p = 4.2610221) confirming a result that we recently reported in a selected adult sample [27]
We have demonstrated, for the first time, that PGF plasma levels are influenced by both genetic and environmental factors
Summary
Placental growth factor (PGF), originally identified in the placenta, is a protein highly homologous to vascular endothelial growth factor (VEGF) [1]. As the specific ligand of the VEGF receptor 1 (Flt-1), PGF has potent angiogenic properties and induces the growth and migration of the endothelial cells (EC) [2]. PGF plays important roles in the maternal vascular function and the remodelling of the maternal vasculature during pregnancy including the uterine spiral arteries which pervade the placenta. Decreased levels of PGF during midgestation have been shown to be predictive of the subsequent development of clinical preeclampsia [4]. PGF expression is normally low in most other organs/tissues, the expression is inducible and required in tissues undergoing pathological angiogenesis [5] including vascularized tumours [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
