Atherosclerosis is a very specific type of artery hardening that occurs due to accumulation of white blood cells and their inflammation of the vessel. Atherosclerosis can cause heart attacks, formation of blood clots and obstruction of major vessels. There are a number of risk factors, including tobacco smoking, high LDL cholesterol, diabetes, vitamin B6 deficiency, high C reactive protein, and many others.
Atherosclerosis is now known to be an immunoinflammatory condition, one which results from inflammation mediated by immune cells. In recent years, mast cells have been found to play an important role in the formation of atherosclerotic lesions, progression and destabilization of the lesion, which in turn causes the more significant clinical effects. In 2004, 66% of men and 47% of women in the US had heart attack or sudden cardiac death as their first symptom of atherosclerotic heart disease.
Endothelial cells line the blood vessels and form the endothelium. In atherosclerotic plaques, monocytes from the blood burrow into the endothelium. They turn into macrophages, a different kind of cell. These macrophages eat certain kinds of cholesterol and start a cycle in inflammation in the vessel wall. Platelets then stick to the inflamed places.
Mast cells are known to have a number of behaviors that affect plaque pathology. Mast cells near plaques release tryptase, which activates endothelial cells through the PAR-2 receptor. This causes a series of events that produces platelet activating factor (PAF). PAF increases the permeability and contraction of the nearby smooth muscle, which can lead to vascular events.
Increased densities of mast cells have been found in the tissue layer overlaying plaques that ruptured. It has been hypothesized that mast cell released histamine could cause coronary spasm, making the plaque more likely to rupture. In a study that looked at 44 autopsy samples of aorta with atherosclerotic lesions, there was a direct correlation found between levels of tryptase and chymase, the amount of collagen in the plaque, and the size of the endothelium involved.
Mast cells that store basic fibroblast growth factor (bFGF) are found in small vessels inside plaques. Histamine may cause leakage from those tiny vessels, which can further make the plaque more likely to rupture. In histamine deficient mice, the plaque area was reduced in size, and expression of genes for NF-kB, matrix metalloproteinases (MMPs), and inflammatory cytokines involved in plaque progression. Histamine is also involved in acute coronary vasospasm that may result in heart attack; this is called Kounis Syndrome.
References:
Simon Kennedy, Junxi Wu, Roger M. Wadsworth, Catherine E. Lawrence, Pasquale Maffia. Mast cells and vascular diseases. Pharmacology & Therapeutics 138 (2013) 53–65.
Ramalho, L. S., Oliveira, L. F., Cavellani, C. L., Ferraz, M. L., de Oliveira, F. A., Miranda Corrêa, R. R., et al. (2012). Role of mast cell chymase and tryptase in the progression of atherosclerosis: study in 44 autopsied cases. Ann Diagn Pathol 17, 28–31.
Lappalainen,H., Laine, P., Pentikäinen,M. O., Sajantila,A.,& Kovanen, P. T. (2004).Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator. Arterioscler Thromb Vasc Biol 24, 1880–1885.
Kounis, N. G., Mazarakis, A., Tsigkas, G., Giannopoulos, S., & Goudevenos, J. (2011). Kounis syndrome: a new twist on an old disease. Future Cardiol 7, 805–824.