Endothelial Dysfunction, vitamin D3 and Masquelier's OPCs

• Excerpt

The endothelium is the inner lining covering the walls of the entire cardiovascular system. Although it is no more than a very thin layer consisting of endothelial cells, the endothelium is, all by itself, a complete organ with a wide range of cardiovascular functions. For one thing, it regulates blood pressure by releasing a gaseous molecule that "tells" the smooth muscle of the blood vessel to relax when the endothelium senses an increase in blood pressure. That gaseous molecule's name is nitrogen oxide, also known as nitric oxide or "NO". When the endothelium doesn't function as it should, its failure to produce an adequate amount of NO is accompanied by the concomitant overproduction of a cytotoxic vasoconstrictor and powerful oxidant named peroxynitrate, also known by the abreviation ONOO−. How do we maintain a healthy balance between NO and ONOO− ?

The non-classical effect of vitamin D3

In 2018 a group of researchers of the Ohio University reported in a study concerning the role of Vitamin D3 in restoring NO/ONOO− imbalance, "there is a large body of observational data that links vitamin D3 to the function of the cardiovascular system. This non-classical effect of vitamin D3 is additional to the more classical role of vitamin D3 on the mineral-calcium metabolism in bone. Clinical studies suggest (somewhat inconsistently) that elevated vitamin D3 levels can lower arterial blood pressure. However, there is a strong correlation between insufficient serum levels of vitamin D3 that are observed in heart failure, myocardial infarction and elevation of arterial blood pressure. In cross-sectional studies [...], a deficiency in vitamin D3 metabolites correlated with hypertension, diabetes mellitus, hyperglyceridemia [high blood sugar] and obesity. [I]

Vitamin D3 acts on the endothelium

That vitamin D3 exerts its beneficial cardiovascular effects via the endothelium is proven by the fact that when one "knocks out" the vitamin D3 receptors on endothelial cells, an elevation of arterial blood pressure is the result. Other studies carried out on spontaneous hypertensive rats have indicated that vitamin D3 administration suppresses endothelium-dependent contraction of the aorta and thus prohibits an undue elevation of arterial blood pressure.  Furthermore, vitamin D3 was shown to have a direct effect on endothelial and smooth muscle cells in the vascular wall and may decrease undue blood clotting, increase the forming of new endothelium and prevent and break down blood clots.

Nanosensors

The Ohio University researchers developed a unique nanomedical method of measurement and analysis to elucidate in situ (right there where things take place) the role of vitamin D3 in the stimulation of a healthy NO/ONOO− ratio in dysfunctional endothelial cells. Nanomedical sensors are needles with an extremely small diameter of 200-300 nanometers. One nanomemeter is equal to one billionth of a metre. The nanosensors used in this study are capable of detecting in near real-time molecular changes of the two signaling molecules, NO and ONOO−, released by the endothelial cells. The sensors are placed just above the surface of single cells that were brought into a dysfunctional state causing a harmful imbalance in concentrations of NO and ONOO−, similar to that found in cases of high blood pressure. The dysfunctional cells were then treated with vitamin D3 to see if this might bring them back to a perfectly functional state and produce a healthy NO/ONOO− balance.

Vitamin D3 restores NO/ONOO− imbalance

The outcome of the study squarely supports the beneficial role of vitamin D3 on vascular health and indicates that this effect is caused  by vitamin D3's action on the endothelium. According to the researchers: "Treatment with vitamin D3, in this cellular model of hypertension, significantly restored bioavailable NO with the concomitant decrease in nitroxidative stress that is associated with high ONOO−. [...] As a net result, vitamin D3 maintains a favorably high ratio of NO/ONOO− in the endothelium with a relatively high concentration of cytoprotective vasorelaxant NO and a relatively low level of cytotoxic vasoconstrictor ONOO−. This favorable kinetics of NO generation and the subsequent low production of ONOO− after stimulation with vitamin D3 are crucial factors in the process of restoring dysfunctional endothelium. In long-term (hours) treatment, vitamin D3 effectively reversed the imbalance between NO and ONOO− in [this] cellular model of hypertension."

It all starts with oxidative stress

The cascade of events leading up to endothelial dysfunction and NO/ONOO− imbalance finds its origin in oxidative stress. As pointed out by the Ohio University's nano-team: "previously published observations have suggested that vitamin D3 deficiency-induced hypertension is associated with vascular oxidative stress" because "oxidative and nitroxidative stress impairs endothelium-dependent relaxation of the blood vessels and is involved in the facilitation of smooth muscles contractions. It has been suggested that oxidative stress is the main source of endothelial damage, and that it is generated by NADPH oxidase – one of the key enzymes of facilitating oxidative stress." So, although vitamin D3 isn't an antioxidant, it decreases the over-expression of NADPH oxidase and another enzyme named Endothelial Nitric Oxide Synthase (eNOS). By decreasing the over-expression of these two enzymes, vitamin D3 indirectly lowers oxidative stress in endothelial cells.

Vitamin D3 and Masquelier's OPCs

In the context of endothelial dysfunction, the link between vitamin D3 and OPCs is obvious and irrefutable. The long standing and vast body of evidence that Masquelier's OPCs are instrumental in microvascular/endothelial homeostasis shows that this authentic botanical extract ranks first in supporting cardiovascular health. The action of OPCs becomes most evident where the vascular system reaches the point of exchange between the blood and the tissues, where it consists of nothing but endothelial cells, i.e. at the level of the capillaries, since it is there that they repair fragility and increase well regulated permeability. Besides this, Masquelier's OPCs are fine antioxidants and, speaking of blood pressure, they speed up normalisation of blood pressure after strenuous exercise. Yet, in light of the vitamin D3 studies, it's obvious that OPCs are fighting an uphill battle when vitamin D3 is deficient, which is, unfortunately, the case in the majority of people living a "Western" style of life. In other words, Masquelier's OPCs and vitamin D3 need each other to optimize cardiovascular health.

Significantly higher doses !!!

While the nanomedical study was performed using a cellular model of hypertension, the  authors concluded that the implications of the influence of vitamin D3 on dysfunctional endothelium are much broader. "The dysfunction of endothelium", so they wrote, "is a common denominator of several cardiovascular diseases, particularly those associated with ischemic events. Therefore, we suggest that vitamin D3 treatment may be of clinical importance in the restoration of dysfunctional cardiac endothelium after heart ischemia, capillary endothelium after brain ischemia, hypovolemia [insuffient quantity of blood and lymph], vasculopathy [vascular abnormalities], diabetes and atherosclerosis. Our suggestion is strongly supported by several clinical studies indicating that vitamin D3, at doses significantly higher than those currently used for the treatment of bone diseases, can be highly beneficial for the treatment of the dysfunctional cardiovascular system." The emphasis was added by yours truly.

[I] Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases; Alamzeb Khan, Hazem Dawoud. Tadeusz Malinski; Department of Chemistry & Biochemistry, Nanomedical Research Laboratories, Ohio University, Athens, OH, USA; International Journal of Nanomedicine, 2018.