This is an excerpt from Advanced Cardiovascular Exercise Physiology-2nd Edition by Denise L. Smith & Bo Fernhall.
Properly functioning endothelium is critical to the health and function of the cardiovascular system. This section briefly describes the major functions of the endothelium. Specific functions are addressed in more depth Âlater in this chapter and in subsequent chapters. As shown in figure 7.4, the vascular endothelium has multiple functions, and Âthese functions are often specific to the site in the vascular tree. The primary functions of the endothelium include
- serving as a selectively permeable barrier to regulate blood–Âtissue exchange,
- regulating vascular tone,
- releasing anticlotting and proclotting Âfactors to control hemostasis,
- participating in inflammatory defense against pathogens, and
- initiating new blood vessel formation (angiogenesis).
The exchange of fluids, nutrients, and gases between the blood and tissues occurs primarily within the capillaries (figure 7.4, #1). The primary role of the endothelium in regulating this exchange is to form a semipermeable membrane that retains blood within the vessel and allows nutrients and gases to move into the tissue. ÂThese functions rely on structural features of the endothelium are due largely to the glycocalyx and the intracellular junctions. While lipid-Âsoluble substances diffuse through the endothelial cells, small, water-Âsoluble substances diffuse through the intracellular junctions. Large molecules, such as immunoglobulins and protein-Âbound hormones, pass from the circulation to the underÂlying tissue via the caveola–Âvesicle system. ÂThese flask-Âshaped structures are actually invaginations into the cell membrane that permit the endothelial cells to take up substances from the blood by the proÂcess of endocytosis. The movement of fluid and nutrients across the endothelium occurs primarily at the capillary level, due to the thinness of the vessel wall.
Vascular tone is determined by the degree of smooth muscle contraction in the tunica media (figure 7.4, #2). When smooth muscle contracts (vasoconstriction), it decreases the diaÂmeter of the blood vessels and decreases blood flow. Conversely, relaxation of the smooth muscle (vasodilation) increases the diaÂmeter of a blood vessel and results in increased blood flow. Endothelium that lines the arteries and arterioles plays a central role in regulating contraction of the smooth muscle cells in the tunica media and thereby helps control blood flow. Endothelial cells respond to changing conditions, especially shear stress, and release chemical mediators that lead to vasodilation (nitric oxide, NO; prostacyclin, PGI2) and vasoconstriction (endothelin) of the smooth muscle. The balance of Âthese mediators plays an imporÂtant role in determining blood flow distribution to variÂous organs. The importance of this role of endothelium is reinforced by the fact that endothelial dysfunction is often assessed by the ability of smooth muscle to vasodilate in response to a stimulus.
ÂFactors released from the endothelium have a potent effect on blood clotting potential (figure 7.4, #3). In fact, some of the same vasodilatory Âfactors, notably NO and PGI2, that cause relaxation of underÂlying smooth muscle are also released into the bloodstream where they have an inhibitory effect on platelet aggregation, making a clot formation less likely. Thus, the release of Âthese Âfactors has the simultaneous and mutually reinforcing effect of increasing blood flow and maintaining blood fluidity. In fact, the endothelium is one of the only surfaces, Âeither natuÂral or synthetic, that can maintain blood in its fluid state during prolonged contact. This ability is due to the presence of heparin sulfate proteoglycan molecules on the surface of endothelial cells (Libby, 2005). ÂUnder certain circumstances, namely vascular injury, endothelium also secretes von Willebrand Âfactor (vWF), which is produced in specialized organelles called Weibel-ÂPalade bodies. Von Willebrand Âfactor promotes platelet adhesion and plays a role in the coagulatory cascade. Thus, the endothelium plays a critical role in maintaining blood fluidity and fostering clot formation. The role of the endothelium in maintaining homeostatic balance is discussed fully in chapter 8.
The endothelium is also essential in the inflammatory and immune defense against pathogens (figure 7.4, #4). In response to injury or invasion, venular endothelium produces adhesion molecules that cause circulating leukocytes to be attached to the endothelium. Several adhesion molecules are involved in causing a leukocyte to adhere to the endothelium. P-Âselectin, which is released from Weibel-ÂPalade bodies, and E-Âselectin cause a loose bond between the leukocyte and the endothelium. Intracellular adhesion molecules (ICAMs) and vascular adhesion molecules (VCAMs) then cause a tighter bonding of the leukocyte and endothelium. FiÂnally, the leukocyte begins to move into the intracellular junction; it then moves into the tissue through the proÂcess of diapedesis. The final step is dependent on platelet–Âendothelial cell adhesion molecules (PECAM). Venular endothelium can also produce large endothelial gaps that allow for increased delivery of immunoglobulins (antibodies) to the tissue to provide an immune response in response to infection. Plasma also passes through Âthese endothelial gaps, leading to the swelling that characterizes inflammation.
The endothelium plays a critical role in the development of new vessel formation, termed angiogenesis (figure 7.4, #5). Capillary sprouting initiates all new blood vessels. Endothelial cells can be stimulated to divide rapidly when Âthere is a need for new vessel formation (for growth or repair or to support new tissue). New vessel formation begins with the breakdown of the basal lamina and the sprouting of the endothelium from the side of a capillary or venule. The cell extensions put out by the endothelium, called pseudopodia, grow Âtoward the stimulus for new blood supply. ÂThese pseudopodia are enlarged by cytoplasmic growth Âuntil they divide into Âdaughter cells. Vacuoles then digest material within the new Âdaughter cells. Eventually the vacuoles of the Âdaughter cells fuse, resulting in a new lumen. The entire proÂcess continues Âuntil the new sprout encounters another capillary to connect to.
Case Study
COVID-19 and the Vascular Endothelium
Sonya is a 36-Âyear-Âold female who enjoys hiking with her Âfamily but does not engage in regular programmed fitness training. She has a BMI of 32 and a resting BP of 126/88 mmHg. Despite trying to practice social distancing as recommended, Sonya developed respiratory symptoms and Âlater tested positive for COVID-19. Sonya’s doctor advised her that her recovery would include allowing time for the lungs and vascular endothelium to heal. Sonya knew that the lungs Âwere affected by COVID-19 but was surprised to hear about the vascular endothelium.
Questions
- How does the SARS-ÂCoV-2 virus affect the endothelium?
- What are the consequences of endothelial disruption with COVID-19?