The endothelium is the innermost of the artery’s three layers. It is formed by cells that cover the inside of our ateries and veins. It is a signal receiving and emitting system.
Endothelial function is a key factor in preserving vascular health, which also serves as a clinical marker for predicting the development and/or result of undesirable disorders.
The endothelium is currently recognized as a dynamic organ with important autocrine and paracrine functions, which allow it to maintain vascular homeostasis through multiple and complex interactions between endothelial cells and the vessel lumen. The main homeostatic functions of the endothelium involve: a) the regulation of vascular tone through a balanced production of vasodilator and vasoconstrictor factors; b) maintaining the fluidity and coagulation of the blood by producing factors that regulate platelet activity, the coagulation cascade and the fibrinolytic system; and c) the production of cytokines and adhesion molecules that regulate vascular inflammatory function (Badimon L, Martínez González J.; Disfunción endotelial. Rev Esp Cardiol. 2006)
Protects endothelial dysfunction caused by excessive oxidative stress as a consequence of genetic, metabolic and external factors.
Endothelial cells have a crucial role in vascular health. Among other things, endothelial cells produce prostacyclin and nitric oxide (NO) (“Harvard Medical School; June 2019) which helps keep the artery open and healthy.
NO was identified as an important endotelial relaxing factor (Moncada et al. 1987) and the role of NO in arterial tone was also established.
This NO has two crucial functions:
- It keeps the arterial lining smooth and slippery, preventing white blood cells and platelets from latching on and causing damaging inflammation and artery-blocking blood clots.
- It relaxes the smooth muscle cells of the artery wall’s middle layer, preventing spasms and keeping arteries open.
In addition to endothelium-dependent vasodilatation, NO also has a number of other critical functions in the vascular system, including inhibition of platelet aggregation, inhibition of endotelial cell adhesion molecule expression, prevention of vascular smooth-muscle cell migration and proliferation, and prevention of intravascular coagulation and thrombosis.
Therefore, NO is an important factor in the maintenance of normal vascular homeostasis and the protection of vessels from injuries induced by atherogenic processes, such as smoothmuscle cell proliferation, platelet aggregation, monocytes adhesion, and oxidative modification of LDL (“Update on Uses and Properties of Citrus Flavonoids: “New Findings in Anticancer, Cardiovascular, and Anti-inflammatory Activity; Journal of Agriculture and Food 1Chemistry”; O. Benavante, J. Castillo 2008).
NO is critical to avoid disorders such as arteriosclerosis through its antiplatelet, antiproliferative and inhibitory effect on inflammatory phenomena (Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. , 109 23 Suppl 1; 2004)
The endothelial dysfunction is currently considered one of the first manifestations of vascular disease, mainly based on the concept of an imbalance in the bioavailability of active substances of endothelial origin, predisposing to inflammation, vasoconstriction, and increased vascular permeability, facilitating platelet aggregation, thrombosis and arteriosclerosis, representing a key early step in the development of atherosclerosis, participating in the progression of plaque and the appearance of atherosclerotic complications.
Therefore, a dysfunctional endothelium has an increased consumption of nitric oxide (NO), which creates favorable conditions for platelet plus leukocyte activation and adhesion, as well as the activation of cytokines that increase the permeability of the vessel wall to oxidized lipoproteins and inflammation mediators.
Oxidative stress is the common condition capable of explaining this deterioration of vascular function mediated by alterations in the NO system (Rajagopalan S et al.; “Angiotensin II-mediated hypertension in the rat increases vascular su-peroxide production via membrane NADH/NADPH oxidase activation”. Contribution to alterations of vasomotor tone. 97; 1996).
During redox imbalance, the superoxide anion (O2 * -) quickly reacts with NO, inactivating it and reducing the vasodilatory capacity of the endothelium.
This biochemical reaction also leads to the production of peroxynitrite, a highly reactive intermediate that favors protein nitration and the oxidative damage of circulating lipids, which is why it is directly related to the oxidative modification of low-density lipoproteins (LDL). and the progression of endothelial damage (Nedeljkovic ZS et al. “Mechanisms of oxidative stress and vascular dysfunction”. 79; 2003),
This finally results in structural damage of the arterial wall which smooth muscle cell proliferation and plaque formation.
Endothelial tissue regulates vascular tone and exerts finely tuned control over cardiovascular homeostasis, with nitric oxide (NO) being one of the best-characterized vasodilator endothelial factors.
The endothelial factors that could release the different extracts and flavonoids are important to explain the vascular relaxing effects.
Studies show that flavonoids can cause vasorelaxation at physiological concentrations. The relaxation observed is largely endotheliumand NO-dependent, although other mechanisms also appear to be involved (Woodman, O. L.; Chan, E. Ch. Vascular and anti-oxidant actions of flavonols and flavones. Clin. Exp. Pharmacol. Physiol. 2004, 31, 786–79).
Inflammation and oxidation
Free radicals oxidize LDL cholesterol, causing a hardening of the plaques in the arterial walls, which, in turn, causes a narrowing of the vessels. These cholesterol lipoproteins accumulate in the tissues.
High levels of C-reactive protein (CRP) in blood is a possible risk indicator. High levels of CRP are an indication of inflammation in the body, being the general response to injury or infection. Injuries to the inside of the artery walls would trigger inflammation and promote plaque growth, thickening of the intimate tunic with plaques containing macrophages filled with lipids, fats, primarily cholesterol.
People with low levels of CRP may have slower-onset atherosclerosis than when they have high levels of CRP.
Antioxidants can make free radicals harmless and protect our cells. Requirement is that we supply our body with enough vitamins and phytonutrients with antioxidant properties. A suitable dietary supplement can protect your blood vessels from inflammation.
OxLDL produces pro-atherogenic effects in endothelial cells by inducing the expression of adhesion molecules, stimulating apoptosis, inducing superoxide anion formation, and impairing protective endothelial nitric oxide formation (Yu, Wong, Lau, Huang, & Yu, 2011)
Generally, the literature is consistent with oxidative stress contributing to the five characteristic microvascular responses to inflammation, namely vasomotor dysfunction (impaired vessel dilation and constriction), leukocyte recruitment, increased vascular permeability, angiogenesis, and thrombosis (“Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the multiethnic study of atherosclerosis”; Am J of Clinical Nutrition; Nettleton et al., 2006)
According to published clinical studies on polyphenols in olive oil and assumed by the EFSA Committee of Experts, these exert antioxidant activity on blood lipids. Oxidation and inflammation are feedback processes that are generated in the walls of the blood vessels, causing the appearance of plaques that end up obstructing them.
Several mechanisms have been proposed to explain how excessive production of ROS leads to vascular pathology. First, ROS are able to promote the oxidation of low-density lipoprotein (LDL) (136, 137). Uptake of oxidatively modified lipoproteins by macrophages transforms these cells into foam cells, which are a key component of atherosclerotic plaques (138, 139). Second, superoxide anion rapidly inactivates endotheliumderived nitric oxide (NO), a molecule with intrinsic antiatherogenic properties, leading to endothelial dysfunction, which is a hallmark of early atherosclerosis
These plaques end up forming in strategic places of the arteries where the high blood pressure ends up sensitizing the walls (the endothelium), producing said inflammation and oxidation.
Generally, the literature is consistent with oxidative stress contributing to the five characteristic microvascular responses to inflammation, namely vasomotor dysfunction (impaired vessel dilation and constriction), leukocyte recruitment, increased vascular permeability, angiogenesis, and thrombosis (Nettleton et al., 2006
A remarkable finding of the study was a significant reduction of the cytokine IL-6, a marker of inflammation High IL-6 concentrations have been associated with increased risk of myocardial infarction (MI) in healthy men. Moreover, IL-6 and its receptor levels have an early peak at the acute phase of MI, likely related to plaque instability (Bacchiega, B.C. et al.; “Interleukin 6 Inhibition and Coronary Artery Disease in a High-Risk Population: A Prospective Community-Based Clinical Study”. J. Am. Heart Assoc. 2017).
In the Health, Aging, and Body Composition study of 2225 participants 70 to 79 years old without baseline cardiovascular disease, IL-6 was significantly associated with all outcomes, including coronary heart disease, stroke, and congestive heart failure (Cesari, M. Inflammatory Markers and Onset of Cardiovascular Events: Results from the Health ABC Study. Circulation 2003).
The relaxation of these walls is essential.