Introduction to the Human Blood Vessels
The human circulatory system consists of blood vessels that transport blood throughout the body.
There are three major types of blood vessels:
- Arteries (Arteries carry the blood away from the heart)
- Veins (Veins carry blood from the capillaries back toward the heart)
- Capillaries (Capillaries allow the exchange of water and chemicals between the blood and the tissues)
The arteries and veins consist of the tunica, a membranous sheath enveloping or lining an organ. The tunica consists of three layers:
- Inner layer (the tunica intima)
- This is the thinnest layer of squamous endothelial cells glued by a polysaccharide intercellular matrix
- Middle layer (the tunica media)
- This is the thickest layer in the arteries of circularly arranged elastic fiber and connective tissue. It is prominent in vascular smooth muscle.
- Outer layer (the tunica adventitia)
- This is the thickest layer in the veins made of entirely connective tissue composed of collagen. The collagen serves to anchor the blood vessel to nearby organs, giving it stability. Nerves are contained in the tunica adventitia.
The Capillaries consist of a layer of endothelium and connective tissue.
The Endothelium of the Tunica Intima
Endothelium is a type of squamous epithelium that lines the interior surface of blood vessels. The endothelium forms an interface between circulating blood in the lumen and the rest of the vessel wall.
Endothelial cells in the blood vessels serve the following functions:
- Barrier function
- The endothelium acts as a barrier between the vessel lumen and surrounding tissue. It controls the passage of materials and the transit of white blood cells into and out of the bloodstream.
- Blood clotting (thrombosis & fibrinolysis)
- The endothelium normally provides a non-thrombogenic surface which is due to the glycocalyx layer atop the endothelium. (See Endothelium Glycocalyx)
- Formation of new blood vessels, also known as angiogenesis
- Vasoconstriction and vasodilation
Maintaining the integrity of the endothelium prevents endothelial dysfunction, which is a hallmark for vascular diseases, including atherosclerosis.
The Endothelial Glycocalyx
The endothelial glycocalyx is a very thin (approximately 1 μm magnitude or .001 millimeters or 0.00003937007874 inches) 1 hydrated gel-like layer on the luminal surface of the vascular endothelium. The thickness of the glycocalyx increases with vascular diameter, at least in the arterial system, ranging from 2 to 3 μm in small arteries 4 to 4.5 μm in carotid arteries. 2
It is commonly referred to as the endothelial glycocalyx layer (EGL) or endothelial surface layer (ESL). 3 4 The glycocalyx is located on the apical surface of vascular endothelial cells which line the lumen.
The endothelial glycocalyx was already visualized some 40 years ago by JH Luft using electron microscopy. 5 The importance and validity of the endothelial glycocalyx as a vital factor in vascular physiology and pathology has increased over the years. 6 7
The name “glycocalyx” means “sweet husk” or “sugar coat”, referring to its high polysaccharide content. The term was initially applied to the polysaccharide matrix coating epithelial cells which is a delicate gel lining inside our arteries.
The glycocalyx is a gel-like coating that acts as a shield for the endothelium and forms the interface between the vessel wall and moving blood. The glycocalyx is held in place to the arterial wall by protein hair-like fibers. The composition of the glycocalyx is not static as there is a balance between biosynthesis and shedding of glycocalyx components.
The glycocalyx is composed of a negatively charged network of proteoglycans, glycoproteins, and glycolipids. 8 Located between the blood stream and the endothelium, the endothelial glycocalyx is an important determinant of vascular permeability. 12 It is able to limit access of certain molecules to the endothelial cell membrane. A dynamic equilibrium exists between the glycocalyx and the flowing blood, continuously affecting composition and thickness of the glycocalyx. In fact, the shear stress applied from blood flow patterns provide the stimulus for the synthesis of the glycosaminoglycans present in the glycocalyx. As would be expected, the more turbulent blood flow patterns around vessel bifurcations and curvatures result in an inherently thinner glycocalyx, which explains the vulnerability of these areas to clot formation.
The endothelial glycocalyx plays a major role in the regulation of endothelial vascular tissue and thus has a variety of biological functions.
- Vascular permeability
- Impenetrable layer
- Glycocalyx serves as a slippery layer to prevent things such as oxidized LDL cholesterol and white blood cells from sticking to the endothelial cells. Once endothelial cells are exposed, then cholesterol plaque may develop.
- Exclusion zone
- Acts as the exclusion zone between blood cells and the endothelium.
- Physical barrier
- Provides a physical barrier against inadvertent adhesion of platelets and leukocytes to the vascular wall. 11
- Modulates red blood cell volume
- Modulation of red blood cell volume in capillaries 12
- Barrier against leakage of certain molecules
- Acts as a barrier against leakage of fluid, proteins and lipids across the vascular wall.
- Dynamic interaction
- Interacts dynamically with blood constituents.
- Natural coagulant regulator
- Regulates coagulation under normal physiological condition 13
- Modulation of adhesion
- Modulates adhesion of inflammatory cells and platelets to the endothelial surface.
- Sensor and mechanotransducer
- Functions as a sensor and mechanotransducer of the fluid shear forces to which the endothelium is exposed.
- Protective enzymes
- Retains protective enzymes (eg. superoxide dismutase).
- Protection of cell membrane
- Cushions the plasma (cell) membrane and protects it from chemical injury.
- Inflammation regulation
- Glycocalyx coating on endothelial walls in blood vessels prevents leukocytes from rolling/binding in healthy states. 14
- Filtration of interstitial fluid
- Affects the filtration of interstitial fluid from capillaries into the interstitial space. 15
- Binding site
- Serves as a significant binding site for antithrombin III (ATIII), tissue factor pathway inhibitor, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and lipoprotein lipase. 16
Natural Substances that are Known to Maintain and Strengthen the Integrity of the Components of the Blood Vessels
The following Tables provide a list of the known natural substances that have been researched and studied for their ability to maintain and strengthen the integrity of the various components of the blood vessels.
Table 1: Natural Substances that Maintain and Strengthen the Integrity of the Arteries
Natural Substances that Maintain and Strengthen the Integrity of the Arteries
Arteries Substance Abstract Reference
Melatonin In the cardiovascular system, melatonin seems to regulate the tone of cerebral arteries 1
Silicon The silicon content of arteries declines in tandem with the progression of the aging process. The aorta and carotid artery of healthy persons contain approximatively 10 times more silicon compared to atheromatous arteries. 2
Vitamin E (Gamma-tocopherol) Both alpha- and gamma-tocopherol decreased platelet aggregation and delayed time to occlusive thrombus (all p < 0.05 vs. control). Both alpha- and gamma-tocopherol decreased arterial superoxide anion generation, lipid peroxidation and LDL oxidation (all p < 0.05 vs. control), and increased endogenous SOD activity (p < 0.05). 3
Hawthorne Hawthorn displays anti-inflammatory effects in arteries 4
Red Clover The authors concluded that an important cardiovascular risk factor - arterial elasticity - which declines during and after menopause, was significantly improved with red clover isoflavones. 5
Table 2: Natural Substances that Maintain and Strengthen the Integrity of the Veins
Natural Substances that Maintain and Strengthen the Integrity of the Veins
Veins Substance Abstact Reference
Gotu Kola Total triterpenic fraction of Centella asiatica (TTFCA) is active on the microcirculation in venous and diabetic microangiopathy. Signs and symptoms of venous hypertension and edema are improved by treatment. The remodeling on collagen synthesis could be one of the possible mechanisms of actions of TTFCA in the remodeling of echolucent (soft; therefore, with risk of thrombosis and embolization) plaques at the carotid and femoral bifurcation. This compound is safe and well tolerated. In conclusion, several actions of TTFCA in vascular diseases makes the use of this compound very interesting in venous and arterial problems. 1
Troxerutin These results showed a marked affinity of troxerutin for the venous wall. The highest uptake in the outer wall region is likely to result from transport through vasa vasorum, owing to the rheologic properties of the drug. The significant medial fluorescence may account for the venous tone improvement with the drug. 2
Aortic Glycosaminoglycans The results obtained were analysed statistically and confirmed the therapeutic effectiveness of Mesoglycan for this type of pathology, particularly for thrombophlebitis where treatment produced early and lasting results. In conclusion, both the experimental findings and the clinical results obtained, confirm the view that Mesoglycan is a drug of choice for the prevention and treatment of venous pathologies. 3
Horse Chestnut Three hours after taking two capsules of Venostasin (600 mg; each capsule containing 50 mg aescin) the capillary filtration coefficient had decreased by 22%, whereas after administration of an identical-looking placebo capsule it rose but slightly over three hours. The difference in the effect of Venostasin and placebo is statistically significant (P = 0.006). The intravascular volume was reduced 5% more after Venostasin than the placebo, but this is not statistically significant. It is concluded that Venostasin has an inhibitory effect on oedema formation via a decrease in transcapillary filtration and thus improves oedema-related symptoms in venous diseases of the legs 4
Hesperidin Hesperidin (especially when used in combination with diosmin) increases venous tone (i.e. this combination strengthens the walls of veins). 5
Table 3: Natural Substances that Maintain and Strengthen the Integrity of the Capillaries
Natural Substances that Maintain and Strengthen the Integrity of the Capillaries
Capillaries Substance Abstact Reference
Diosmin Diosmin (and hesperidin) were found to maintain the integrity of the endothelium (lining) of capillaries. 1
Oligomeric Proanthocyanidins (OPCs) The authors studied cerebral capillaries, aorta and cardiac muscle capillaries. It could be shown that previous treatment of animals with procyanidolic oligomers (OPCs) prevented the permeability increase produced by collagenase injection. 2
Rutin Rutin helps to strengthen the capillaries. 3
Horse Chestnut Escin, a constituent of Horse Chestnut, reduces capillary fragility. 4
Grape Seeds Free radicals scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. 5
Gotu Kola Gotu Kola was shown to inhibit the inflammatory process which may provoke hypertrophy in scars and improves the capillary permeability. 6
Hesperidin Hesperidin (and diosmin) were found to maintain the integrity of the endothelium (lining) of capillaries. 7
Table 4: Natural Substances that Maintain and Strengthen the Integrity of the Endothelium
Natural Substances that Maintain and Strengthen the Integrity of the Endothelium
Endothelium Substance Abstact Reference
Arginine We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio. 1
Silicon Findings demonstrated that Si both modifies the characteristics of endothelial relaxants and attenuates smooth muscle cell responsiveness to NO. Si-induced reduced NO association with elevated endothelium-derived hyperpolarizing factor (EDHF) in response to ACh, together with reduced NO sensitization, might have clinical importance in cardiovascular pathology. 2
Folic Acid Folic acid significantly improves endothelial function in otherwise healthy cigarette smokers. This provides a potential therapeutic tool in attenuating the atheromatous process in this group. 3
Vitamin C A prospective interventional study was performed. In 15 healthy male subjects (mean age, 24.4 +/-2.5 years old). They studied FMD in the brachial artery by using high-resolution ultrasound. The vascular effects of moderate-term oral supplementation with vitamin C (1.0 g/day) and vitamin E (500 mg/day) were determined during reactive hyperemia, which causes endothelium-dependent FMD. They performed a vascular function study 3 times including before vitamin supplement, after 25 days of vitamin supplement, and 4 weeks after the cessation of the vitamin supplement. The flow-mediated dilator response measurements were repeated twice a day before vitamin supplements, and the repeatability obtained from these measurements was found acceptable (variability of FMD <2%). The oral antioxidant vitamin supplement significantly restored FMD (3.8 +/-2.2% vs 5.9 +/-2.5%; p<0.05), however, this effect disappeared 4 weeks after the vitamin supplementations ended. The combined usual dosage of vitamins C and E supplements was found to improve the endothelial function in chronic smokers. 4
Vitamin E The combined usual dosage of vitamins C and E supplements was found to improve the endothelial function in chronic smokers. 5
Horse Chestnut By maintaining an intact endothelium during in vivo blood stasis in the lower limbs and preventing neutrophil recruitment, adherence and activation, aescine (horse chestnut) could prevent the resulting alterations of the venous wall. These results could explain at least in part the potential benefit of the drug in the prevention of venous insufficiency. 6
Hawthorn Hawthorn improves the health of endothelial cells that line arteries. 7
Pycnogenol This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline hypertensive, hyperglycemic and hyperlipidemic subjects. 8
Salvia miltiorrhiza Bunge (Dan Shen) Salvia miltiorrhiza Bunge, a traditional Chinese herbal medicine, is often used for prevention and treatment of cardiovascular disorders such as atherosclerosis. Endothelial cell hyperpermeability is implicated in inflammation and subsequent ischemic reperfusion injury and atherosclerosis. Data from this study suggest that one of the mechanisms S. miltiorrhiza exerts its pharmacological effect is through its modulation of endothelial cell permeability. 9
Table 5: Natural Substance that Repair and Strengthen the Endothelial Glycocalyx
Natural Substance that Repair and Strengthen the Endothelial Glycocalyx
Glycocalyx Substance Abstact Reference
Rhamnan Sulphate (Arterosil(TM)) A 2013 study corroborated the ability of Rhamnan sulphate to repair the glycocalyx. The researchers reported that rhamnan sulfate enhances the endothelial glycocalyx and decreases the LDL permeability of human coronary artery endothelial cells in vitro. 1
Table 6: Summary of Natural Substances that Maintain and Strengthen the Integrity of the Blood Vessels
Summary of Natural Substances that Maintain and Strengthen the Integrity of the Blood Vessels
Summary of Blood Vessels Substance Arteries Veins Capillaries Endothelium Glycocalyx Totals
Aortic Glycosaminoglycans X 1
Arginine X 1
Diosmin X 1
Folic Acid X 1
Gotu Kola X X 2
Grape Seeds X 1
Hawthorne X X 2
Hesperidin X X 2
Horse Chestnut X X X 3
Melatonin X 1
Oligomeric Proanthocyanidins (OPCs) X 1
Red Clover X 1
Rhamnan Sulphate (Arterosil) X 1
Rutin X 1
Silicon X X 2
Troxerutin X 1
Vitamin C X 1
Vitamin E (Gamma-tocopherol) X X 2
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