Science Olympics: The effects of exercise on circulation and gene regulation

After watching displays of astounding athletic prowess in the 2016 Olympics, I was inspired to take a closer look at the science behind exercise training, recovery, and injury with a focus on the importance of blood vessels during exercise.

Let’s start with some basic training: Why are blood vessels important for exercise?

Muscles need oxygen and nutrients to breakdown fats and carbohydrates for energy and the main delivery system to provide these is blood vessels.  Under normal conditions, a delicate balance is kept between quiescence and remodeling in blood vasculature to maintain a baseline level of muscle activity, but that balance is upset with physical stress such as exercising due to an increased demand for energy and the components required to make that energy.  The “angiogenic switch” is a popular term for the point at which blood vessels change from a quiescent state to an active remodeling state, such as in tumorigenesis [1].  Chemical regulation of angiogenesis is well-researched and includes studies on how growth factors (e.g. VEGFA, bFGF, PDGFB, ANGPT1/2), cytokines, chemokines, and enzymes influence various steps of angiogenesis.  More recently, there has been growing interest on determining how mechanical influences such as muscle contractions might regulate angiogenesis.  This research mainly involves determining how factors involved in environment sensing (e.g. integrins, ion channels, sensory receptors) regulate angiogenic promotion or inhibition through signaling transduction.  Current research seems focused at the cellular level with gene regulation in the spotlight [2].

Angiogenic sprints: Acute effects of exercise on circulation

Almost immediately upon exercising, the metabolic demands of muscles change.  One way your body ensures it gets what it needs quickly is by opening capillaries in exercising muscles that are normally closed when resting.  Another way is by promoting vasoconstriction in tissues nonessential to the activity thereby shunting that blood to the active tissues and typically also the brain.  Concurrently, energy production in exercising muscles creates a hypoxic microenvironment full of vasodilating byproducts like adenosine, CO₂, lactic acid, and hydrogen ions that encourage increased blood flow to those areas.  Again, blood vessels need to transduce these external signals and turn them into biochemical ones and again, gene regulation seems to be key here [3, 4].  Upon signaling, blood vessels need to be physically flexible enough to constrict or dilate as demanded.  So in effect, exercising is like stretching for our blood vessels and it keeps them flexible, which helps stave age-related vascular dysfunctions such as cardiovascular disease, hypertension, macular degeneration, and solid tumor progression [5].  Additionally, having that increased blood flow also benefits the brain both acutely (with increased acuity during and immediately after exercising) and chronically with regular exercise (through boosts in hippocampal oxygen levels and brain adaptations that protect from neurodegenerative diseases) [6–9].

Blood vessel marathons: Chronic effects of exercise on circulation

One of the long-term benefits of regular exercise is a boost in hippocampal power.  During exercise, the body shunts blood to essential tissues like active muscles and the brain, and with that increased blood flow comes an increase in O₂, which promotes brain cell growth [10, 11], The hippocampus is one of the few regions in the adult brain where neurogenesis still occurs [12] and the hippocampus happens to be crucial for certain kinds of memory formation and emotional behavior.  While many effects of exercising eventually revert when you stop, the cells that proliferate during exercise survive and persist.  Now, the functional benefits of having all these new brain cells is still unclear, but studies suggest they may influence learning and memory [13–18].  Furthermore, the heart adapts to regular exercising over time by building more cardiac muscle for stronger beats, thereby eventually decreasing both active and resting heart rates while maintaining optimal cardiovascular output.  This means that you’ll also be able to exercise harder and longer in the future.

What are your thoughts on exercising, vascular biology, or gene expression regulation?  About what would you like to know more?  To conduct your own research on these topics or any others, visit sciencellonline.com for helpful products.

Related products:

GeneQuery Human qPCR arrays for gene expression profiling: Angiogenesis, Endothelial Cell Biology, Endothelial Cell Differentiation, Endothelial Cell Heterogeneity, Shear Stress and Mechanotransduction, Hypoxia Response, HIF1 Signaling, Neural Development and Regeneration, Neural Plasticity, Alzheimer’s Disease, Cardiovascular Disease

Human Primary Cells: endothelial cells, cardiac myocytes, neurons, stem cell derived cells

References:

1. SA Olenich, et al.  Temporal response of positive and negative regulators in response to acute and chronic exercise training in mice.  J Physiol. 2013 Oct 15; 591(Pt 20): 5157–5169.
2. P Strzyz.  Gene regulation: May the force be with you.  Nat Rev Genet. 2016 Sep;17(9):505. doi: 10.1038/nrg.2016.103. Epub 2016 Aug 1.
3. P Fraisl, et al.  Regulation of angiogenesis by oxygen and metabolism.  Dev Cell. 2009 Feb;16(2):167-79. doi: 10.1016/j.devcel.2009.01.003.
4. BL Krock, et al.  Hypoxia-induced angiogenesis: Good and evil.  Genes Cancer. 2011 Dec;2(12):1117-33.
5. DR Seals.  Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries.  J Appl Physiol (1985). 2014 Sep 1; 117(5): 425–439.
6. JS Querido & AW Sheel.  Regulation of cerebral blood flow during exercise.  Sports Med. 2007;37(9):765-82.
7. MD Delp, et al.  Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine.  J Physiol. 2001 Jun 15; 533(Pt 3): 849–859.
8. NJ Kirk-Sanchez & EL McGough.  Physical exercise and cognitive performance in the elderly: Current perspectives.  Clin Interv Aging. 2014; 9: 51–62.
9. E Ang, et al.  Neurodegenerative diseases: Exercising toward neurogenesis and neuroregeneration.  Front Aging Neurosci. 2010; 2: 25.
10. H van Praag, et al.  Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus.  Nat Neurosci. 1999 Mar;2(3):266-70.
11. H van Praag, et al.  Exercise enhances learning and hippocampal neurogenesis in aged mice.  J Neurosci. 2005 Sep 21; 25(38): 8680–8685.
12. PS Eriksson, et al.  Neurogenesis in the adult human hippocampus.  Nat Med. 1998 Nov;4(11):1313-7.
13. FH Gage.  Mammalian neural stem cells.  Science. 2000 Feb 25;287(5457):1433-8.
14. H Suh, et al.  Signaling in adult neurogenesis.  Annu Rev Cell Dev Biol. 2009;25:253-75.
15. W Deng, et al.  New neurons and new memories: How does adult hippocampal neurogenesis affect learning and memory?  Nat Rev Neurosci. 2010 May; 11(5): 339–350.
16. KI Erickson, et al.  Exercise training increases size of hippocampus and improves memory.  Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22.
17. C Vivar, et al.  All about running: Synaptic plasticity, growth factors and adult hippocampal neurogenesis.  Curr Top Behav Neurosci. 2013;15:189-210.
18. C Zhao, et al.  Mechanisms and functional implications of adult neurogenesis.  Cell. 2008 Feb 22;132(4):645-60.