TRYPTASE INHIBITOR AND HEMOPEXIN
RESEARCH AND DESIGN

WHAT IS TRYPTASE?

The temperature restricted ingredients manufactured by Caviar Biotec (excluding Caviar Water) naturally contain key bioactives, including a Tryptase Inhibitor enzyme. Tryptase is the most abundant protein in the human mast cells and was characterised in 19812. Tryptase promotes inflammation as part of a human immunological response and many of the age related diseases in humans start from Tryptase activated chronic inflammatory conditions

Tryptase in the major protease that degranulated when a Mast Cell is activated, and therefore elevated Tryptase levels are a known indicator of an inflamed state and is known to trigger an inflammatory response from the immune system when released by human mast cells.

Tryptase is the major protein stored and secreted by human mast cells. 

The amount and property of this serine peptidase varies by mast cell subtype and tissue origin. 

Once secreted, Tryptase promotes inflammation, Extra cellular matrix destruction, and tissue remodeling by several mechanisms, including destroying pro-coagulant, matrix, growth and differentiation factors, and activating proteinase-activated receptors, urokinase, metalloproteinases (MMPS’s), and angiotensin (see below). 

Tryptase also modulates immune responses by hydrolyzing chemokines and cytokines. 

Human Tryptase

WHAT IS A TRYPTASE INHIBITOR

Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin complex

Tryptase is one of the main serine-proteinases located in the secretory granules of mast cells, and is released through degranulation, which is involved in the pathogenesis of allergic inflammatory disease, cardiovascular diseases, lung fibrosis and tumor. Therefore, inhibitors targeting tryptase represent a new direction for the treatment of allergic inflammatory disease and other pro inflammatory age related diseases.

In 2019, the Mass Spectrometry data analysis (Mascot Database) undertaken by St Andrews University, reveled a significantly high match between Leech derived Tryptase Inhibitor in trypsin complex (LdTI) and the three main Caviar Biotec ingredients, Pure Caviar Oil, Insoluble Caviar Extract and Soluble Caviar Extract; and it was on the basis of this discovery that Caviar Biotec has undertaken the extensive ground breaking research into peptides and enzymes derived from the Acipenseriformes placenta and roe.          

IMFLAMMAGING, HUMAN AGE RELATED DISEASE & ELEVATED TRYPTASE

Inflamm-aging (also known as inflammaging or inflamm-ageing) is a chronic low-grade inflammation that develops with advanced age. It is believed to accelerate the process of biological aging and to worsen many age-related diseases.

Tryptase is a known precursor to inflammaging and increased  levels of Tryptase are found within the blood, as age increases and normally detected when a diagnosis of age related disease is known.

Examples of aging-associated diseases are atherosclerosis and cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension and Alzheimer’s disease. The incidence of all of these diseases increases exponentially with age and increased levels of Tryptase in the blood.

CARDIOVASCULAR HEALTH

Cardiovascular disease has long been accepted to be in some part related to inflammatory status, for example pro-fibrotic effects on blood vessel walls and atherosclerotic plaques. Elevated tryptase levels have been associated with patients that suffer from a cardiac event at follow up in a study on cardiovascular health.

RESPIRATORY HEALTH

It is well understood that mast cells play an important role in asthma, their presence is elevated in this chronic inflammatory condition. In Chronic Obstructive Pulmonary Disease (COPD) tryptase levels in the sputum correlate with the severity of the disease.

SKIN HEALTH

Tryptase and other mast cell mediators have been studied in relation to skin ageing and inflammatory conditions of the skin including scleroderma, psoriasis and pemphigus. In addition the role of tryptase in successful wound healing and skin remodelling has been demonstrated.

MUSCULOSKELETAL

Although many different chemicals in the cells play a role in the chronic inflammation associated with rheumatoid arthritis, mast cell mediators including tryptase play a prominent role. Increased numbers of mast cells and associated tryptase bound to heparin have been detected in the synovium of patients with rheumatoid arthritis.

NEURODEGENERATION

The role of mast cells in neurodegenerative diseases is being increasingly recognised1 and elevated mast cell presence has been proven in mice with Alheimer’s Disease2. Recently, mast cells have emerged as potential key players in both neuroinflammation and neurodegenerative diseases. Mast cells have been found in situ with amyloid deposition in Alzeimer’s Disease and “an inhibitor of mast cell function was shown to reduce cognitive decline in AD patients”.1

CANCER & GUT

There is a link between mast cells and metastasis in lung cancer related conditions. Metastasis is the spread of cancer from one area to another. Exosomes are released by cancer cells which are then taken up by mast cells, the bodies defence mechanism, which then releases tryptase that causes further complications. Caviar produce counteracts this in the body’s processor tools to dissemble this reactive system and stabilise the disease.

WHAT ARE MMPS AND HOW DO THEY RELATE TO MAST CELLS AND TRYPTASE?

Previously introduced, mast cells and the action of their messengers including tryptase operate within the extra cellular matrix. Another group of proteases, named matrix metalloproteinases (MMPs) also exist in this extra cellular matrix and play an important role in the regulation of the integrity and composition in the matrix itself1. MMPs are considered to be responsible for the disruption and degradation of the extracellular matrix, they are activated by proteases produced by the mast cells, including tryptase. MMPs also influence the proliferation, migration, differentiation and death of the cells that exist within the matrix1. There are at least 15 different types of MMPs identified2, it is understood that the balance of these MMPs within the matrix can influence how cells and the body behave in various disease states, they are known to play an important role in determining disease severity and the onset of acute events.

1. Hermans M, Lennep JRV, van Daele P, Bot I, Mast Cells in Cardiovascular Disease: From Bench to Bedside, International Journal of Molecular Sciences, 2019, 10, e3395, https://www.ncbi. nlm.nih.gov/pubmed/31295950
2. Mohajeri M, Kovanen PT, Bianconi V, Pirro M, Cicero AFG, Sahebkar A, Mast cell tryptase – Marker and maker of cardiovascular diseases, Pharmacology & Therapeutics, 2019, 199, 91-110, https://www.ncbi.nlm.nih.gov/pubmed/30877022
3. Morici N, Farioli L, Losappio LM, Colombo G, Nichelatti M, Preziosi D, Micarelli G, Oliva F, Gianattasio C, Klugmann S, Pastorello E, Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease, Open Heart, 2016, 3, e000472, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051537/
4.Djuric T, Zivkovic M, Overview of MMP Biology and Gene Associations in Human Diseases, Intech Open, 2017, 1, 3-33.
5. Johnson J, Jackson C, Angelini G, George S, Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques, Atherosclerosis, Thrombosis, and Vascular Biology, 1998, 18, 1707-1715.