Development of blood vessels - the Why and How?
By Sarah Willis, PhD
The vascular system is made up of a network of pathways to carry oxygenated blood throughout the body and deliver deoxygenated blood back to the heart.
As we know, blood travels out of heart through the aorta and to the rest of the body via the arteries, smaller arteries, arterioles, then gas is exchanged (oxygen for carbon dioxide) at the capillaries, followed by returning to the heart via venules, veins, vena cavas (inferior and superior) into the right atrium of the heart. When going further into the composition of our vessels, there are 3 main layers; the tunica adventitia, the outermost layer that contains nerves and tiny vessels which delivers oxygen and nutrients to cells, removes waste, and offers structure and support; the middle layer - tunica media, which contains smooth muscle cells to contract and relax the vessels for constriction and dilation and blood flow/pressure regulation; and the tunica intima (inner layer), made up of the endothelial cells (like skin of vessels) and basement membrane.
This article is focused on the development of blood vessels – which leads us to the question of WHY does my body want/need to develop new blood vessels? The answer is relatively simple, because when we deliver more blood (by increasing blood flow…also with new blood vessels), then there is more oxygen available to the tissues in that area, which will improve our energy metabolism and allow our bodies to adapt to more efficient use of energy – and yes, we should also get faster.
The more interesting question is HOW do we develop new blood vessels? The straightforward answer is via angiogenesis, a process of new blood vessel formation. The further you read along, the more you should be able to understand the basics of this process. See, angiogenesis is necessary for our survival, development, and for wound healing – it is a lifelong process that begins before birth and continues all our life. Angiogenesis is a process of budding and formation of new blood vessels from pre-existing microvessels, migration, proliferation, and survival. New vessels start out similar to capillaries, very small in diameter of 5-8 μm. This process is important for the treatment of cardiovascular disorders, cancer, diabetes, obesity, etc. There are 2 main processes, 1) growth of capillaries (sprouting of capillaries from pre-existing vessels), and 2) blood vessel remodeling (enlargement of existing vessels). Events that must occur for this to happen are the activation of endothelial cells and vasodilation of parent (original) blood vessel, followed by digestion of the basement membrane and migration of endothelial cells from parent vessel toward the site where angiogenesis is required by chemotactic derived from monocytes, platelets, mast cells, and neutrophils.
Ok, so let’s try it again…angiogenesis is a process regulated by a tissue’s need for oxygen (lack of oxygen would stimulate the process). When endothelial cells in the vessels are under stress (can be mechanical forces – shear stress, pressure, tension), this can alter structure and function of the endothelial cells, leading to angiogenic events and microvessel formation. There are 3 phases of how this happens.
Phase 1 = endothelial cell activation and increased endothelial permeability in response to stress conditions, i.e., hypoxia-lack of oxygen, or ischemia-lack of blood flow. In this phase, under hypoxic conditions the hypoxia-inducible factor 1 (HIF-1) protein complex works to return body to homeostasis and in this case vascular endothelial growth factor (VEGF) induces vasoconstriction and increases endothelial permeability via endothelial nitric oxide production. Further, plasma proteins allow for a scaffold of fibrin-rich network, and cytokines are released from various sources.
Phase 2 is endothelial cell migration and proliferation; migration from the normal site which is facilitated by MMP activity and release of growth factors (i.e., VEGF, FGF, IGF-1…). In general, the VEGF family of growth factors has a specific function in proliferation and migration of endothelial cells.
Phase 3 is sprouting and maturation of endothelial cells, similar to cell differentiation and remodeling. Some endothelial cells, called tip cells (growth buds), are selected for sprouting – including phenotypic changes in cells that provide invasive behavior, motor efficiency, activation of proteases, locally digested basal membrane. Then we have new blood vessels – like capillaries in the beginning of a new microvessel formation to expand the availability of oxygen to the tissues.
The main themes here are: increased permeability, cell proliferation, cell migration, and sprouting/maturation of endothelial cells. Let’s dive briefly back into these for clarification:
Increased permeability --- which can be a bad thing (related to inflammatory response), but in this situation it helps to increase flow of blood from capillaries into tissues spaces = a good thing for delivering blood with oxygen
Cell proliferation --- multiplication and reproduction of endothelial cells to expand the cell population
Cell migration --- movement of cell or group of cells (part of homeostasis – vital for proper cardiovascular function)
Sprouting and maturation of endothelial cells --- needed to proliferate and form new vessel structures
As an overview, angiogenesis occurs when the endothelial cells lining the blood vessels multiply forming a line towards the area that needs a new blood supply. This process is triggered in areas that need oxygen in response to high levels of vascular endothelial growth factor (VEGF), a signaling molecule. Further, our endothelial cells improve permeability (increasing flow into tissue spaces), multiply/replicate to increase in number, then migrate, sprout, and mature to form new vessel structures.
Now in practical terms, HOW do we stimulate the process of angiogenesis?
First and foremost, regular exercise helps the body grow new blood vessels (hypoxia – lack of oxygen, and ischemia – lack of blood flow). The stress of exercise is important for promoting this process of angiogenesis to develop an increasingly more efficient transport of oxygen. When we exercise, our skeletal muscles have an increased demand for oxygen and thus, need more blood. This causes a response in our body to stimulate the arteries to release nitric oxide which relaxes smooth muscle cells (vasodilation) to improve blood flow. All of this stimulates capillary growth and remodeling of vasculature. A general recommendation is to have at least 30 min of exercise 3 times a week for 6 weeks to improve this process. We know that with our training, we exceed this recommendation – but the process remains the same and we now understand better how this process works. Since the greater the oxygen demand we create (high-intensity exercise, altitude exposure, high stimulus, etc.), the more time we signal this process. Other ways to stimulate the development of blood vessels = drink black or green tea, take iron supplements or eat iron-rich foods (especially if anemic), decrease stress, eat more omega 3 fatty acids, wear compression socks/elevate legs, take vitamin C, consume high levels of magnesium (spinach, avocado, dark chocolate, pumpkin seeds, almonds, black beans, cashews, bananas, edamame), besides medicinal interventions/quit smoking/dry brushing body. Furthermore, pomegranate juice (which has nitrate – a potent vasodilator, which facilitates blood flow) can open up the arteries, and B complex vitamins (B6 and B12, along with B3) are valuable for vessel health. Continuing to drink plenty of water is of great general importance which naturally helps blood flow around and boost circulation.
We continue to have more insight now into our fueling choices and understand how these foods contribute to improving our cardiovascular health and optimizing our performance. Enjoy the process!