After being discharged, a person who has had COVID-19 is readmitted a month later for multiple thromboses in the legs and lung. He suffers from a state of dysfunction of the endothelium, the cells that line the arteries.
Another person confined by COVID-19 has just had a thrombosis in one eye. Others, months later, have thromboses in different locations. These are endothelial dysfunctions.
The state of endothelial dysfunction is characterised by a disrupted endothelium, in the first case due to the virus and in the second case possibly due to prolonged sedentary lifestyle. Both factors promote procoagulant, pro-inflammatory, pro-oxidant and proliferative activity which also promotes atherogenesis and cholesterol plaque formation. Now many people who are inactive for forty days are going to have altered cholesterol numbers. When someone is operated on, surgeons order immediate mobility. Lack of exercise causes epithelial dysfunction, and less production or availability of nitric oxide (NO) which we will see their functions.
Among the mechanisms proposed to explain this state of dysfunction, oxidative stress and chronic low-grade inflammation caused by insufficient dietary antioxidant intake and lack of exercise, aggravated by sustained stress during the pandemic, are cited as the most important.
The main pathways by which the endothelium appears to improve its functions, and which are effectively activated by daily exercise, are nitric oxide, endothelin-1, neuregulin-1, prostacyclin, vascular endothelial growth factor and NOx. I incorporate these latinisms as a reminder that biological processes cannot be simplified when accounting for them. Complexity is reacted to with rejection because we are inundated with simplifications that are moulding our minds towards the simple.
Exercise enhances the ability of endothelial cells to filter and metabolise certain components of circulating plasma, as well as counteracting endothelial inflammatory processes and the consequent optimisation of the balance between oxidants and antioxidants.
It is now known that one of the initial episodes in the development of atherosclerosis is a phenomenon known as endothelial dysfunction, so we will come out of house arrest with elevated cholesterol.
The layer of cells lining the inside of the vessels synthesises and releases a wide variety of substances, including vasoactive substances that regulate vascular tone, blood pressure and blood flow to each organ; substances involved in coagulation, in fibrinolysis that would hinder the production of clots, small fibrils that clog vessels because platelets stick to them. They also control and regulate inflammatory and immune reactions that are profoundly altered in this pandemic in severe cases. The virus penetrates the endothelium and destroys or damages it, which explains thrombosis long after it has healed.
When our way of life includes daily exercise, the balance between reactive oxygen species and reactive nitrogen species, i.e. the dreaded free radicals, is maintained. These are involved in the oxidation and nitrosylation of proteins and lipids, which are also part of the utilisation of proteins and lipids by our metabolism. The production of free radicals cannot be stopped while we use what we eat and expend it in the various functions of living, and in the production of energy in the mitochondria. Exercise has the virtue of producing antioxidants, in addition to those that the body itself already has.
The role of the endothelium is modulated by a series of receptors, gateways or anchor sites present in its membranes for numerous molecules including proteins, hormones, lipid transport particles, metabolites, as well as cell-cell binding proteins and receptors that govern cell-cell interactions.
The main function of the endothelium is the regulation of blood flow and tissue perfusion through changes in vessel diameter and vascular tone, which is one of the main functions of daily physical exercise. It is the best pill, almost the only pill, against ageing, and the best pill against hypertension. Hypertonia equals high blood pressure.
In order not to oversimplify, and to get used to living with the complex and get out of our way of living immersed in simplicities, there are other substances to control vascular tone by producing prostacyclin, and endothelium-derived hyperpolarising factor, all vasodilatory factors. The vasoconstrictor state is mediated by the production of endothelin-1, angiotensin II and thromboxane A2. It is precisely one of these substances that we use to lower hypertension, angiotensin II, the gateway for angiotensin I, which is the same one used by the virus to enter cells.
NO - nitric oxide - is able to diffuse between cells and tissues due to its gaseous nature. NO also has antioxidant, anti-inflammatory, anti-platelet aggregation, and anti-proliferative effects on vascular smooth muscle cells, as it forms cholesterol plaque when altered.
Reduced NO bioavailability, increased oxidative stress, increased expression of prothrombotic and pro-inflammatory factors, and increased vasoreactivity are known as endothelial dysfunction, all of which occur during stress and to the highest degree during severe cov-19 infection. Once these functions are impaired, the person may relapse with symptoms indicative of these altered factors.
It also causes increased endothelial permeability which promotes the passage and deposition of LDL particles, cholesterol, in the arteries. I have often explained that stress, sedentary life, poor nutrition contained in many diets and milk substitutes, smoking and other toxins keep us in a state of low-level inflammation that is not asymptomatic. In fact, ageing is being in low-level inflammation, and exercise is a superb producer of anti-inflammatory, cytokine and cholesterol-lowering substances.
In the case of dyslipidaemia, a low level of HDL, the "good" cholesterol, correlates with impaired endothelial function. The functions of HDL lipoprotein include endothelial protection and as a particle with antioxidant and anti-inflammatory properties that transports cholesterol from the arteries to the liver, which in turn transforms it into bile and expels it in the faeces.
The effect of exercise on the endothelium and other organs and muscles seems to depend not only on vasodilation and increased blood perfusion, but also on improved communication between the endothelial cells of these organs and the underlying cells beneath them, which would improve renal, cardiac, glandular, cognitive function and overall homeostasis. Daily exercise improves the functionality of the lung epithelia and helps to achieve higher lung capacity and better CO2-oxygen exchange capacity. Thus, the potential damage to general health that confinement may have caused to both children and adults is appreciated.
NO is synthesised by vascular endothelial cells and acts as a major vasodilator and regulator of a number of local homeostatic processes. As a vasodilator, its mechanism of action is based on direct smooth muscle cell relaxation at the local level. NO also acts as an inhibitor of platelet adhesion and aggregation which is executed to form clots, inhibitor of the proliferation of smooth muscle cells which if formed would start to deposit cholesterol and plaques appear, as well as inhibitor of the expression of adhesion molecules, which together contribute to coagulation and even as an antioxidant by offsetting the effects of superoxide anion, i.e. anti-ageing.
In addition, Different lifestyle habits, such as smoking and dietary patterns low in dietary antioxidants or high in carbohydrates and/or saturated fats, can increase the production of free radicals leading to stress.. Increased levels of physical activity and exercise-induced cardiorespiratory fitness are directly related to reduced morbidity and mortality from coronary heart disease and all types of diseases.. Among the possible mechanisms underlying the benefits of exercise in the general population is the improvement of endothelial function. This is why gyms should not have to pay VAT and be free for children and young people, which would generate huge savings for the state.
Exercise is a potent NO stimulus for the whole body. Exercise has an endothelial regenerative potential, because, following their production in the bone marrow, they migrate through the systemic circulation to sites of injury or tissue turnover to replace highly damaged or dead vascular endothelial cells. In addition, they have the ability to modulate different complex processes of endothelial and myocardial regeneration, such as angiogenesis, myogenesis and cardiomyocyte apoptosis and as a dynamic mechanism of long-term vascular protection, preventing atherosclerosis and cardiovascular disease.
José Antonio Rodríguez Piedrabuena
Specialist in psychiatry and psychoanalysis. Specialist in management training, group and couple therapies.