VEGF Expression

VEGF Protein


VEGF is a growth factor that has been linked to both curing and causing numerous diseases. Its expression through exercise may provide insight on its role in the human body.

Vascular endothelial growth factor (VEGF) is plays a major role in many physiological functions and has disease implications. VEGF is a key regulator of angiogenesis, the process of building new blood vessels. In a previous research blog post, Controlling Alzheimer's Risk, it was mentioned that increased VEGF in the brain leads to a decreased risk of Alzheimer's. VEGF counters the loss of the brain's blood vessels that results from natural aging. However, the past decade has seen a flurry of debate regarding VEGF's role in cancer.  

Cancer patients have been found to have increased levels of VEGF around their tumors. VEGF inhibitors are suppressed by malignant cells. This allows new blood vessels to penetrate through the developing tumor. Thus, VEGF suppressors have been a focus of several cancer-treating drugs. Their performance in cancer patients has shown mixed results. In some trials the anti-VEGF drugs have, in concert with chemotherapy, decreased tumors. Other trials have found that anti-VEGF drugs make the tumor more potent.

VEGF upregulation, an increase in cellular VEGF receptors, has been linked to brain edema, tumors, anti-inflammatory diseases and age-related macular degeneration, the leading cause of blindness.

VEGF levels fluctuate with the menstrual cycle is essential for embryonic development.  VEGF is necessary for postnatal development. Partial VEGF inhibition in neonatal mice resulted in stunted growth, increased mortality and impaired organ function, notably the liver (VEGF is required for growth and survival in neonatal mice. 1999: HP Gerber, et al.).  

In a developed human when is VEGF expressed? VEGF is expressed during hypoxia, oxygen suppression, and exercise. However, the mechanism of VEGF expression differs between exercise and hypoxia. A study published in 2010 offers insight into exercise's mechanism of VGEF expression (Exercise-induced VEGF transcriptional activation in brain, lung and skeletal muscle, 2010, Kechun Tang, et al.).

In this study, mice were subject to an hour of exercise on a treadmill and two hours in 6% oxygen. VGEF expression was measured  with transcriptors, mRNA and the actual protein. VGEF levels rise in response to exercise in the brain, lungs and skeletal muscle, but not the liver or heart. Results can be seen in the graph below.

 One hour of exercise signals an increase in transcriptional-regulated VEGF gene expression in brain and lung.  Mice were subjected to a 1-h exercise bout (24 M/min, 10° incline) before the collection of non-skeletal muscle organs and measurement of VEGF transcriptional activity, mRNA and protein levels compared to non-exercised (Resting) mice.

In contrast, hypoxia resulted in higher protein expression in the brain only. Additional differences can be seen in the areas of the brain that saw elevated VEGF expressed. VEGF expression in exercised mice was elevated in the hippocampus only. Mice subjected to hypoxia saw expression elevated in the hippocampus, frontal cortex and striatum.

Exercise increases VGEF protein level in the hippocampus only.  Trends can be observed between Luciferase, mRNA and VEGF level.

Interestingly, exercise produced the same linear relationship between the levels of luciferase transcriptor, VEGF mRNA and VEGF protein across organs suggesting they share a similar cellular mechanism of expression. This may play an impact when looking at the role played by VEGF or VEGF inhibitor in disease treatment.

Please share any thoughts you have on the implications of this research or updates on the medical research being done on VEGF.

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