Mast cell tryptase – Marker and maker of cardiovascular diseases

Mohajeri, Mohammad; Kovanen, Petri T.; Bianconi, Vanessa; Pirro, Matteo; Cicero, A.F.G.; Sahebkar, Amirhossein

doi:10.1016/j.pharmthera.2019.03.008

Cited by 24 publications

(13 citation statements)

References 319 publications

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“…Yet, when compared with macrophages and T cells, we can measure at least the plasma level of a molecule, the tryptase, which is derived from mast cells and from mast cells only. However, determination of the level of circulating tryptase reflects both the constitutive mast cell-derived and the mast cell activation-dependent release of tryptase, and, moreover, it reflects the amount tryptase released by the totality of mast cells in the human body [134]. When compared with the total number of mast cells in the human body, the number of mast cells in the coronary arteries must be extremely small—maybe one per-mille or even much less.…”

Section: Mast Cells As Effector Cells In Atherogenesismentioning

confidence: 99%

Mast Cells as Potential Accelerators of Human Atherosclerosis—From Early to Late Lesions

Kovanen

2019

IJMS

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Mast cells are present in atherosclerotic lesions throughout their development. The process of atherogenesis itself is characterized by infiltration and retention of cholesterol-containing blood-derived low-density lipoprotein (LDL) particles in the intimal layer of the arterial wall, where the particles become modified and ingested by macrophages, resulting in the formation of cholesterol-filled foam cells. Provided the blood-derived high-density lipoproteins (HDL) particles are able to efficiently carry cholesterol from the foam cells back to the circulation, the early lesions may stay stable or even disappear. However, the modified LDL particles also trigger a permanent local inflammatory reaction characterized by the presence of activated macrophages, T cells, and mast cells, which drive lesion progression. Then, the HDL particles become modified and unable to remove cholesterol from the foam cells. Ultimately, the aging foam cells die and form a necrotic lipid core. In such advanced lesions, the lipid core is separated from the circulating blood by a collagenous cap, which may become thin and fragile and susceptible to rupture, so causing an acute atherothrombotic event. Regarding the potential contribution of mast cells in the initiation and progression of atherosclerotic lesions, immunohistochemical studies in autopsied human subjects and studies in cell culture systems and in atherosclerotic mouse models have collectively provided evidence that the compounds released by activated mast cells may promote atherogenesis at various steps along the path of lesion development. This review focuses on the presence of activated mast cells in human atherosclerotic lesions. Moreover, some of the molecular mechanisms potentially governing activation and effector functions of mast cells in such lesions are presented and discussed.

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Section: Mast Cells As Effector Cells In Atherogenesismentioning

confidence: 99%

Mast Cells as Potential Accelerators of Human Atherosclerosis—From Early to Late Lesions

Kovanen

2019

IJMS

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“…They have been associated with several cardiovascular diseases including atherosclerosis, myocardial infarction and aneurysms 16 , pathologies in which mast cells are contributing to the pathogenesis essentially through the release of their granule content. Importantly, circulating Tryptase was recently suggested to be a marker for cardiovascular diseases 23 . Moreover, mast cells have been previously involved in diastolic dysfunction induced by ovariectomy in rats 24 and diabetic cardiomyopathy in streptozotocin-treated mice 25 .…”

Section: Discussionmentioning

confidence: 99%

Mast cells participate in the development of diastolic dysfunction in diabetic obese mice

Guimbal¹,

Cornuault

Hollier

et al. 2020

Preprint

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Rational: Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. However, to date, its pathophysiology remains poorly understood. Objective: Our goal was to investigate the role of microvessel disease in the pathophysiology of diastolic dysfunction. Findings: To do so, we used Leptin receptor deficient (Lepr db/db ) female mice as a model of diastolic dysfunction. In these mice, the increased end diastolic pressure (EDP) signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Lepr db/db and control female mice confirmed endothelial dysfunction and systemic inflammation but also revealed a strong increase in several mast cell markers (notably FceR1a, Tryptase and Chymase). We then histologically confirmed an accumulation of activated mast cells in the heart of Lepr db/db mice. Importantly, mast cell degranulation inhibition reduced EDP, vascular leakage and leucocyte infiltration in Lepr db/db mice. Conclusion: Mast cells play a critical role in the development of cardiac microvessel disease and diastolic dysfunction.

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“…In addition to biogenic amine production, MCs contribute to the inflammatory process by releasing a wide range of highly bioactive effectors after degranulation, tryptases being the most abundant (66). Tryptases are implicated in the pathogenesis of allergic inflammatory diseases, cardiovascular disease, lung fibrosis, and even cancer, so their inhibition may be useful therapeutically (66,67). Interestingly, tick-derived protease inhibitor (TdPI) was identified in the salivary glands of R. appendiculatus and was shown to suppress the activity of human β-tryptase and trypsin and, to a lesser extent, plasmin (68).…”

Section: Itch and Painmentioning

confidence: 99%

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

et al. 2020

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Immunodeficiency disorders and autoimmune diseases are common, but a lack of effective targeted drugs and the side-effects of existing drugs have stimulated interest in finding therapeutic alternatives. Naturally derived substances are a recognized source of novel drugs, and tick saliva is increasingly recognized as a rich source of bioactive molecules with specific functions. Ticks use their saliva to overcome the innate and adaptive host immune systems. Their saliva is a rich cocktail of molecules including proteins, peptides, lipid derivatives, and recently discovered non-coding RNAs that inhibit or modulate vertebrate immune reactions. A number of tick saliva and/or salivary gland molecules have been characterized and shown to be promising candidates for drug development for vertebrate immune diseases. However, further validation of these molecules at the molecular, cellular, and organism levels is now required to progress lead candidates to clinical testing. In this paper, we review the data on the immunopharmacological aspects of tick salivary compounds characterized in vitro and/or in vivo and present recent findings on non-coding RNAs that might be exploitable as immunomodulatory therapies.

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Mast cell tryptase – Marker and maker of cardiovascular diseases

Cited by 24 publications

References 319 publications

Mast Cells as Potential Accelerators of Human Atherosclerosis—From Early to Late Lesions

Mast Cells as Potential Accelerators of Human Atherosclerosis—From Early to Late Lesions

Mast cells participate in the development of diastolic dysfunction in diabetic obese mice

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

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