Editing Vulnerable plaque (section)

==Formation==
Researchers have found that accumulation of [[white blood cells]], especially [[macrophages]], termed [[atherosclerosis|inflammation]], in the walls of the arteries leads to the development of "soft" or vulnerable plaque, which when released aggressively promotes blood clotting.

Current research and thinking relating to the formation of vulnerable plaques (see [[atherosclerosis]]) is:<ref name="texasheartinstitute.org">{{Cite web|url=http://www.texasheartinstitute.org/HIC/Topics/Cond/vulplaq.cfm|title=Vulnerable Plaque - Texas Heart Institute Heart Information Center|website=www.texasheartinstitute.org|language=en|access-date=2017-03-28}}</ref>
* Hyperlipidemia, hypertension, smoking, homocysteine, hemodynamic factors, toxins, viruses, and/or immune reactions results in chronic endothelial injury, dysfunction, and increased permeability.<ref name=":0">{{Cite book|title=Robbins and Cotran pathologic basis of disease|others=Kumar, Vinay, 1944-, Abbas, Abul K.,, Aster, Jon C.,, Perkins, James A.|year = 2014|isbn=9781455726134|edition= Ninth |location=Philadelphia, PA|oclc=879416939}}</ref>
* [[Lipoprotein]] [[LDL]] particles, which carry fats (including the fat [[cholesterol]] made by every human cell) within the water/[[blood plasma|plasma]] portion of the blood stream, are absorbed into the intima, past the [[endothelium]] lining, some of the [[Low-Density Lipoprotein|LDL-lipoprotein]] particles become oxidized and this attracts macrophages that uptake the particles. This process typically starts in childhood. To be specific: oxidized lipoprotein particles in the artery wall are an irritant which causes the release of proteins (called [[cytokine]]s) which attract monocyte white blood cells (white blood cells are the inflammatory cells within the body).
* The cytokines induce the endothelial cells lining the artery wall to display adhesion molecules that attract immune-system white blood cells (to be specific, [[monocytes]]).
* The monocytes squeeze into the artery wall. Once inside, they transform into [[macrophages]] which will ingest the oxidized lipoprotein particles.
* The macrophages sometimes become so overloaded with oxidized lipoprotein particles, the cholesterol contained therein and membrane-laden that they are called foam cells. Some of these cells die in place, releasing their fat and cholesterol-laden membranes into the intercellular space. This attracts more macrophages and smooth muscle cell migration and proliferation.
* Smooth muscle cells migrate from the media to the intima, proliferate, and develop an extracellular matrix made up of collagen and proteoglycans.<ref name=":0" />
* In some regions of increased macrophage activity, macrophage-induced-enzymes erode away the fibrous membrane beneath the endothelium so that the cover separating the plaque from blood flow in the [[Lumen (anatomy)|lumen]] becomes thin and fragile.
* Mechanical stretching and contraction of the artery, with each heart beat, i.e. the pulse, results in rupture of the thin covering membrane, spewing clot-promoting plaque contents into the blood stream.
* The clotting system reacts and forms clots both on the particles shed into the blood stream and locally over the rupture. The clot, if large enough, can block all blood flow. Since all the blood, within seconds, passes through 5-micrometre capillaries, any particles much larger than 5 micrometres block blood flow. (most of the occlusions are too small to see by angiography).
* Most ruptures and clotting events are too small to produce symptoms, though they still produce heart muscle damage, a slow progressive process resulting in [[ischemic heart disease]], the most common basis for [[congestive heart failure]].
* The clot organizes and contracts over time, leaving behind narrowing(s) called stenoses. These narrowing(s) are responsible for the symptoms of the disease and are identified, after the fact, by the changes seen on [[cardiac stress test|stress tests]] and [[angiography]], and treated with [[Coronary artery bypass surgery|bypass surgery]] and/or [[angioplasty]], with or without [[stents]].

When this inflammation is combined with other stresses, such as high blood pressure (increased mechanical stretching and contraction of the arteries with each heart beat), it can cause the thin covering over the plaque to split, spilling the contents of the vulnerable plaque into the bloodstream. Recent studies have shown [[cholesterol crystal]]s within the plaque play a key role in splitting the plaque and also inducing inflammation.<ref>{{cite journal|last1=Janoudi|first1=Abed|last2=Shamoun|first2=Fadi E.|last3=Kalavakunta|first3=Jagadeesh K.|last4=Abela|first4=George S.|title=Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque|journal=European Heart Journal|date=1 July 2016|volume=37|issue=25|pages=1959–1967|doi=10.1093/eurheartj/ehv653|pmid=26705388|doi-access=free}}</ref> The sticky cytokines on the artery wall capture blood cells (mainly [[platelet]]s) that accumulate at the site of injury. When these cells clump together, they form a thrombus, sometimes large enough to block the artery.

The most frequent cause of a cardiac event following rupture of a vulnerable plaque is [[Thrombus|blood clotting]] on top of the site of the ruptured plaque that blocks the lumen of the [[artery]], thereby stopping blood flow to the tissues the artery supplies.

Upon rupture, atheroma tissue debris may spill into the blood stream; this debris has cholesterol crystals<ref>{{cite journal|last1=Abela|first1=GS|last2=Kalavakunta|first2=JK|last3=Janoudi|first3=A|last4=Leffler|first4=D|last5=Dhar|first5=G|last6=Salehi|first6=N|last7=Cohn|first7=J|last8=Shah|first8=I|last9=Karve|first9=M|last10=Kotaru|first10=VPK|last11=Gupta|first11=V|last12=David|first12=S|last13=Narisetty|first13=KK|last14=Rich|first14=M|last15=Vanderberg|first15=A|last16=Pathak|first16=DR|last17=Shamoun|first17=FE|title=Frequency of Cholesterol Crystals in Culprit Coronary Artery Aspirate During Acute Myocardial Infarction and Their Relation to Inflammation and Myocardial Injury.|journal=The American Journal of Cardiology|date=31 August 2017|doi=10.1016/j.amjcard.2017.07.075|pmid=28867129|volume=120|issue=10|pages=1699–1707}}</ref> and other material which is often too large (over 5 micrometers) to pass on through the [[capillary|capillaries]] downstream. In this, the usual situation, the debris obstruct smaller downstream branches of the artery resulting in temporary to permanent end artery/capillary closure with loss of blood supply to, and death of, the previously supplied tissues. A severe case of this can be seen during angioplasty in the slow clearance of injected contrast down the artery lumen. This situation is often termed non-reflow.

In addition, [[atheroma]] rupture may allow bleeding from the lumen into the inner tissue of the atheroma, making the atheroma size suddenly increase and protrude into the lumen of the artery, producing lumen [[stenosis|narrowing]] or even total obstruction.