Placental growth factor (PlGF) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''PGF''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. Placental growth factor (PGF) is a member of the VEGF (

vascular endothelial growth factor Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...

) sub-family - a key molecule in

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splittin ...

and

vasculogenesis Vasculogenesis is the process of blood vessel formation, occurring by a '' de novo'' production of endothelial cells. It is sometimes paired with angiogenesis, as the first stage of the formation of the vascular network, closely followed by an ...

, in particular during

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

. The main source of PGF during pregnancy is the

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...

trophoblast The trophoblast (from Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the p ...

. PGF is also expressed in many other tissues, including the villous

. The placental growth factor (PGF) gene is a protein-coding gene and a member of the vascular endothelial growth factor (VEGF) family. The PGF gene is expressed only in human umbilical vein endothelial cells (HUVE) and the placenta. PGF is ultimately associated with angiogenesis. Specifically, PGF plays a role in trophoblast growth and differentiation. Trophoblast cells, specifically extravillous trophoblast cells, are responsible for invading the uterine wall and the maternal spiral arteries. The extravillous trophoblast cells produce a blood vessel of larger diameter for the developing fetus that is independent of maternal vasoconstriction. This is essential for increased

blood flow Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously m ...

and reduced resistance. Proper development of blood vessels in the placenta is crucial for the higher blood requirement of the fetus later in pregnancy. Under normal physiologic conditions, PGF is also expressed at a low level in other organs including the heart, lung, thyroid, and skeletal muscle.

Isoform tissue specificity

There are three isoforms of this protein: PGF-1, PGF-2, PGF-3. PGF-1 is specifically found in the colon as well as mammary carcinomas, while PGF-2 is only found in early placenta up until the 8th week of development. PGF-2 is the only isoform able to bind to heparin. PGF-3 is found mainly in placental tissues.

Clinical significance

Placental growth factor-expression within human

atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...

lesions is associated with

plaque Plaque may refer to: Commemorations or awards * Commemorative plaque, a plate or tablet fixed to a wall to mark an event, person, etc. * Memorial Plaque (medallion), issued to next-of-kin of dead British military personnel after World War I * Pl ...

inflammation and neovascular growth. Serum levels of PGF and sFlt-1 (soluble fms-like tyrosine kinase-1, also known as soluble VEGF receptor-1) are altered in women with

preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...

. Studies show that in both early and late onset preeclampsia, maternal serum levels of sFlt-1 are higher and PGF lower in women presenting with preeclampsia. In addition, placental sFlt-1 levels were significantly increased and PGF decreased in women with preeclampsia as compared to those with uncomplicated pregnancies. This suggests that placental concentrations of sFlt-1 and PGF mirror the maternal serum changes. This is consistent with the view that the

is the main source of sFlt-1 and PGF during pregnancy.¹ PGF is a potential biomarker for preeclampsia, a condition in which blood vessels in the placenta are too narrow, resulting in high blood pressure. As mentioned before, extravillous trophoblast cells invade maternal arteries. Improper differentiation may result in hypo-invasion of these arteries and thus failure to widen enough. Studies have found low levels of PGF in women who were diagnosed with preeclampsia later in their pregnancy.

Associated diseases

Placental insufficiency, otherwise known as uteroplacental vascular insufficiency, results from insufficient blood supply to the placenta. This disease is characterized by an alteration in the PGF gene and its GPCR and ERK signaling pathways. Alterations in the PGF and the PGF receptor mRNA expression prevent the normal development of placental vasculature. Twin-to-Twin transfusion syndrome is another disease associated with the PGF gene. This is a rare disease occurring primarily in identical twins where blood from one twin is transferred to the other. Typically, the twin whose blood is being transferred is born smaller and with anemia while the other twin is born larger with too much blood and at increased risk for heart failure. The PGF gene pathways primarily affected are the TGF-Beta pathway and AKT signaling pathway.

Isoform tissue specificity

Clinical significance

Associated diseases

References

Further reading