Mast cell disease in the age of COVID-19: Part 2
It is difficult to overstate the role mast cells play in the various functions of the cardiovascular system.
There are a variety of presentations of heart disease in mast cell patients. Many mast cell mediators directly act upon the cardiovascular system and the heart.
Despite the well known association between allergic reactions and low blood pressure, hypertension is not uncommon in mast cell patients. Mast cell mediators directly impact blood pressure. Histamine can increase blood pressure by binding the H2 receptor. 9a,11b-PGF2, formed by deterioration of PGD2, a mast cell mediator, can also increase blood pressure. [i]
Mast cells release renin to participate in the renin-angiotensin system, one of the mechanisms by which the body regulates blood pressure. In addition to renin, chymase and carboxypeptidase A affect the level of angiotensin II and therefore blood pressure. [i]
A number of mediators are vasodilating and can induce tachycardia, such as prostaglandin D2; vasoactive intestinal peptide (VIP); platelet activating factor (PAF); IL-6 and nitric oxide. [i]
Leukotriene C4, adrenomedullin, tryptase and chymase are all involved in the lifecycle of aneurysms. [ii]
Mast cells are linked to coronary artery disease. They encourage the development of atherosclerotic plaques, affecting blood flow. They are also involved in the rupture of these lesions, triggering an emergent coronary event. [ii]
Mast cell degranulation can trigger Kounis Syndrome, an acute coronary event that similarly affects circulation. [iii]
Some mediators are linked directly to heart failure: tryptase; histamine; PAF; IL-10; tumor necrosis factor (TNF); IL-4; IL-6; fibroblast growth factor (FGF); TGFB (transforming growth factor beta). In patients with heart failure, production and release of catecholamines, including epinephrine and norepinephrine, can become secondarily dysregulated. [i]
Improper control of epinephrine and norepinephrine can have huge consequences on mast cell disease, and the body, generally. Elevated epinephrine levels increase the risk for long QT syndrome, coronary vasospasm, and myocardial ischemia, when lack of blood flow can damage the heart. [iii] High norepinephrine has been linked to sudden cardiac death, though not specifically in the mast cell community. [iv]
|Histamine||Coronary vasoconstriction, activation of platelets, increase expression of tissue factor|
|Chymase||Activation of interstitial collagenase, gelatinase, stromelysin resulting in plaque rupture, generation of angiotensin II, a powerful vasoconstrictor|
|Cathepsin D||Generation of angiotensin II, a powerful vasoconstrictor|
|Leukotrienes (LTC4, LTD4, LTE4)||Powerful vasoconstrictor, levels increased during acute unstable angina|
|Tryptase||Activation of interstitial collagenase, gelatinase, stromelysin resulting in plaque rupture|
|Thromboxane||Platelet aggregation, vasoconstriction|
|PAF||Vasoconstriction, aggregation of platelets|
Author’s note: the effects of mast cell disease and COVID-19 on the cardiovascular system is extremely complicated and requires multiple posts to cover everything. Subsequent posts will address Kounis Syndrome, management of cardiovascular conditions, and how cardiovascular dysfunction affects people with COVID-19.
[i] Kolck UW, et al. (2016). Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research, x, 1-10.
[ii] Kennedy S, et al. (2013). Mast cells and vascular diseases. Pharmacology & Therapeutics, 138, 53-65.
[iii] Kounis NG. (2016). Kounis Syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med, 54(10), 1545-1559.
[iv] Florea VG, Cohn JN. (2014). The autonomic nervous system and heart failure. Circulation Research, 114, 1815-1826.