The Endothelium is a single layer of endothelial cells lines the entire vascular and lymphatic system, from the heart to the smallest capillaries. In adults, approximately ten trillion cells form an almost 1 kg organ and covers a total surface area of 4000 to 7000 square meters - the size of a football field.
In the past, the endothelium was considered inert, described as a `layer of nucleated cellophane', with only non-reactive barrier properties, such as presentation of a non-thrombogenic surface for blood flow and guarding against pro-inflammatory insults. However, it is now becoming clear that endothelial cells actively and reactively participate in haemostasis and immune and inflammatory reactions.
As a barrier, the endothelium is semipermeable and regulates the transfer of small and large molecules into and out of the blood. Endothelial cells are dynamic and have metabolic and synthetic functions. They regulate vascular tone via production of nitric oxide, endothelin and prostaglandins and are involved in the manifestations of atherogenesis, autoimmune diseases and infectious processes. They produce and react to various cytokines and adhesion molecules and it is now clear that they can mount anti- and pro-inflammatory and protective responses depending on environmental conditions and are key immunoreactive cells. Endothelial cells exert significant autocrine, paracrine and endocrine actions and influence smooth muscle cells, platelets and peripheral leucocytes.
Endothelial dysfunction or activation also contributes to a variety of disease states.7
The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases.
After conducting a recent study connecting COVID-19 and the function of the endothelium, Prof. Dr. Frank Ruschitzka, Department of Cardiology, University Hospital Zurich, stated:
"Patients suffering from hypertension, diabetes, heart failure or coronary heart diseases have one thing in common – their endothelial function is markedly impaired. If patients such as these become infected with SARS-COV-2, they will be particularly at risk, as their already weakened endothelial function will diminish even further."15
"Through our study, we are now able to provide evidence to back up our hypothesis that COVID-19 is not only able to affect the lungs, but also the blood vessels in different organs. COVID is a systemic inflammation of the blood vessels and we may now also refer to the disease as COVID-Endotheliitis."15
N2 Pharmaceuticals is a SMART Scotland award winner. The company is based in Roslin Innovation Centre and is developing N2-01, an injectable drug from the meat of Blue mussels. N2 Pharmaceuticals was established in the UK in 2013 with the goal of bringing the drug to the UK and worldwide markets.
N2-01 was invented by the company's founder and developed in collaboration with scientists from the Institute of Experimental Medicine and the State Academy of Veterinary Medicine in St.Petersburg, Russia.
N2-01 is a mixture of amino acids and short peptides. It is a natural composition, without artificial components, derived from the meat of blue mussels through a process of enzyme acid hydrolysis.
N2-01 was already registered for veterinary use in Russia as an injectable medicine in 2010.
N2-01 has proven, both in laboratory settings and clinical usage, to reduce the level of endothelial dysfunction:
Chronic eNOS overexpression in the endothelium of mice resulted in resistance to LPS-induced hypotension, lung injury, and death.8
Most importantly, N2-01 proved to be effective in numerous conditions related to endothelial dysfunction when used on more than 25,000 animals:
COVID-19 is an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality.
Numerous recent publications link the severity and mortality of COVID-19 to the level of endothelial dysfunction (ED). 1-6
Whilst development of vaccines targeting the virus is a long-term preventative measure, treating endothelial dysfunction is a quick and direct response for disease management that could reduce mortality rate and prevent severe onset of the disease.
N2-01 was already registered in Russia as an injectable veterinary medicine. It has proven, both in laboratory settings and in clinic, to reduce the level of endothelial dysfunction.
When studied on human endothelial cells N2-01 influences the factors responsible for onset and severity of ARDS such as VCAM-1, iCAM-1 and NO (Nitric Oxide).
N2-01 proved to reduce vascular permeability (vascular leakage) in mice that is also linked to ARDS.
In addition, N2-01 proved to be effective against Porcine Circovirus Type 2 (PCV-2), when it was used on more than 1,000 piglets on the RusBelgo farm in Russia. No vaccine existed at the time. As a monotherapy the usage of N2-01 reduced mortality from more than 50% to 6%. The pathogenesis and symptoms of PCV-2 are similar to COVID-19: endothelial and epithelial barrier disruption, hyperpermeability, cough, lung oedema, severe respiratory distress.
The medicine has already been registered for veterinary use in Russia in 2010 under the leadership of the current CEO. N2-01 proved to be effective in numerous conditions related to endothelial dysfunction, when used on more than 25,000 companion and food producing animals by practicing veterinarians:
All of this makes us believe that N2-01 could be beneficial in treating patients with COVID-19 through stabilizing the endothelium.
It is proven that a number of other life-threatening conditions such as sepsis, cancer, kidney failure and even aging per se are directly related to the function of endothelium 12,13.
N2-01 has proven, both in laboratory settings and during its usage on animals, to reduce the level of endothelial dysfunction.
N2 Pharmaceuticals believe that there is a high chance that N2-01 could be effective in treating people with conditions related to endothelial dysfunction, because:
N2 Pharmaceuticals Limited, a Scotland based company, have developed N2-01, a unique injectable medicine derived from extracts of Mytilus edulis (Blue mussels), which was approved for veterinary use in Russia in 2010 under the leadership of the current CEO.
N2-01 was used for years by Russian veterinarians in numerous seemingly unrelated conditions such as:
Only recently, after receiving a grant from the Scottish government to continue its research in the UK, N2 Pharmaceuticals discovered that N2-01 reduces the level of endothelial dysfunction and vascular permeability, which connects together all these pathologies.
N2 Pharmaceuticals was founded in 2013 by the current CEO Nikolay Solovyev, in order to realize N2-01's enormous potential in veterinary as well as human medicine around the world.
In 2018 N2 Pharmaceuticals won a SMART Scotland grant and relocated to Roslin Innovation Centre in Edinburgh.
The invention has numerous patents in the UK, EU, USA and Russia.
After successfully discovering, developing and bringing N2-01 onto the Russian market, N2 Pharma team made it their personal goal to realise N2-01's enormous potential in veterinary as well as human medicine around the world.
