Atheroma: Difference between revisions

| causes = [[Hyperlipidemia]], [[hypertriglyceridemia]], [[hypercholesterolemia]]

An '''atheroma''', or '''atheromatous plaque''', is an abnormal and reversible accumulation of material in the [[tunica intima|inner layer]] of an [[arterial]] wall.<ref>{{cite journal |last1=Lusis |first1=Aldons J. |title=Atherosclerosis |journal=Nature |date=September 2000 |volume=407 |issue=6801 |pages=233–241 |doi=10.1038/35025203 |pmid=11001066 |pmc=2826222 }}</ref><ref>{{Cite journal|last1=Francis|first1=Andrew A|last2=Pierce|first2=Grant N|date=2011|title=An integrated approach for the mechanisms responsible for atherosclerotic plaque regression|journal=Experimental & Clinical Cardiology|volume=16|issue=3|pages=77–86|issn=1205-6626|pmc=3209544|pmid=22065938}}</ref>

The material consists of mostly [[macrophage|macrophage cells]],<ref name="pmid20376052">{{cite journal |last1=Hotamisligil |first1=Gökhan S |title=Endoplasmic reticulum stress and atherosclerosis |journal=Nature Medicine |date=April 2010 |volume=16 |issue=4 |pages=396–399 |doi=10.1038/nm0410-396 |pmid=20376052 |pmc=2897068 }}</ref><ref name="pmid22356914">{{cite journal |last1=Oh |first1=Jisu |last2=Riek |first2=Amy E. |last3=Weng |first3=Sherry |last4=Petty |first4=Marvin |last5=Kim |first5=David |last6=Colonna |first6=Marco |last7=Cella |first7=Marina |last8=Bernal-Mizrachi |first8=Carlos |title=Endoplasmic Reticulum Stress Controls M2 Macrophage Differentiation and Foam Cell Formation |journal=Journal of Biological Chemistry |date=6 April 2012 |volume=287 |issue=15 |pages=11629–11641 |doi=10.1074/jbc.M111.338673 |pmid=22356914 |pmc=3320912 |doi-access=free }}</ref> or debris, containing [[lipids]], calcium and a variable amount of fibrous [[connective tissue]]. The accumulated material forms a swelling in the artery wall, which may intrude into the [[Lumen (anatomy)|lumen]] of the artery, [[stenosis|narrowing]] it and restricting blood flow. Atheroma is the [[pathological]] basis for the disease entity [[atherosclerosis]], a subtype of [[arteriosclerosis]].<ref>{{factCite journal |last1=dos Santos |first1=Vanessa Prado |last2=Pozzan |first2=Geanete |last3=Castelli |first3=Valter |last4=Caffaro |first4=Roberto Augusto |title=Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference? |journal=Jornal Vascular Brasileiro |date=September2021 2020|volume=20 |pages=e20200211 |doi=10.1590/1677-5449.200211 |issn=1677-5449 |pmc=8276643 |pmid=34290756}}</ref>

For most people, the first symptoms result from atheroma progression within the [[coronary arteries|heart arteries]], most commonly resulting in a [[myocardial infarction|heart attack]] and ensuing debility. The heart arteries are difficult to track because (a) they are small (from about 5&nbsp;mm down to microscopic), (b) they are hidden deep within the chest and (c) they never stop moving. Additionally, all mass-applied clinical strategies focus on both (a) minimal cost and (b) the overall safety of the procedure. Therefore, existing diagnostic strategies for detecting atheroma and tracking response to treatment have been extremely limited. The methods most commonly relied upon, patient symptoms and [[cardiac stress testing]], do not detect any symptoms of the problem until atheromatous disease is very advanced because arteries enlarge, not constrict, in response to increasing atheroma.<ref name=pmid3574413>{{cite journal |last1=Glagov |first1=Seymour |last2=Weisenberg |first2=Elliot |last3=Zarins |first3=Christopher K. |last4=Stankunavicius |first4=Regina |last5=Kolettis |first5=George J. |title=Compensatory Enlargement of Human Atherosclerotic Coronary Arteries |journal=New England Journal of Medicine |date=28 May 1987 |volume=316 |issue=22 |pages=1371–1375 |doi=10.1056/NEJM198705283162204 |pmid=3574413 }}</ref> It is plaque ruptures, producing debris and clots which obstruct blood flow downstream, sometimes also locally (as seen on [[angiogram]]s), which reduce/stop blood flow. Yet these events occur suddenly and are not revealed in advance by either [[Cardiac stress test|stress tests]]<ref>{{Cite web |title=Stress test - Mayo Clinic |url=https://www.mayoclinic.org/tests-procedures/stress-test/about/pac-20385234 |access-date=2023-10-24 |website=www.mayoclinic.org |language=en}}</ref> or [[angiogram]]s.<ref>{{cnCite journal |last=Darrow |first=Mark D. |date=February1999-01-15 |title=Ordering and Understanding the Exercise Stress Test |url=https://www.aafp.org/pubs/afp/issues/1999/0115/p401.html |journal=American Family Physician |language=en-US |volume=59 |issue=2 |pages=401–410|pmid=9930131 2021}}</ref><ref>{{Cite web |title=Coronary CTA Should Be the Initial Test in Most Patients With Stable Chest Pain: PRO |url=https://www.acc.org/Latest-in-Cardiology/Articles/2018/05/21/06/37/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2018%2f05%2f21%2f06%2f37%2fCoronary-CTA-PRO |access-date=2023-10-24 |website=American College of Cardiology}}</ref>

The healthy epicardial coronary artery consists of three layers, the [[tunica intima]], media, and [[adventitia]].<ref name=Emed>{{EMedicine|article|153647|Coronary Artery Atherosclerosis}}</ref><ref>{{cite journal |last1=Waller |first1=Bruce F. |last2=Orr |first2=Charles M. |last3=Slack |first3=John D. |last4=Pinkerton |first4=Cass A. |last5=Van Tassel |first5=James |last6=Peters |first6=Thomas |title=Anatomy, histology, and pathology of coronary arteries: A review relevant to new interventional and imaging techniques-Part I |journal=Clinical Cardiology |date=June 1992 |volume=15 |issue=6 |pages=451–457 |doi=10.1002/clc.4960150613 |pmid=1617826 |s2cid=12034096 |doi-access=free }}</ref> Atheroma and changes in the artery wall usually result in small [[aneurysm]]s (enlargements) just large enough to compensate for the extra wall thickness with no change in the lumen diameter. However, eventually, typically as a result of rupture of [[vulnerable plaque]]s and clots within the lumen over the plaque, [[stenosis]] (narrowing) of the vessel develops in some areas. Less frequently, the artery enlarges so much that a gross aneurysmal enlargement of the artery results. All three results are often observed, at different locations, within the same individual.<ref>{{factCite journal |last1=Jebari-Benslaiman |first1=Shifa |last2=Galicia-García |first2=Unai |last3=Larrea-Sebal |first3=Asier |last4=Olaetxea |first4=Javier Rekondo |last5=Alloza |first5=Iraide |last6=Vandenbroeck |first6=Koen |last7=Benito-Vicente |first7=Asier |last8=Martín |first8=César |date=September2022-03-20 2020|title=Pathophysiology of Atherosclerosis |journal=International Journal of Molecular Sciences |volume=23 |issue=6 |pages=3346 |doi=10.3390/ijms23063346 |issn=1422-0067 |pmc=8954705 |pmid=35328769 |doi-access=free }}</ref><ref>{{Cite web |title=Thoracic aortic aneurysm - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/thoracic-aortic-aneurysm/symptoms-causes/syc-20350188 |access-date=2023-10-24 |website=Mayo Clinic |language=en}}</ref>

Over time, atheromata usually progress in size and thickness and induce the surrounding muscular central region (the media) of the [[artery]] to stretch out, which is termed ''remodeling''. Typically, typicallyremodeling occurs just enough to compensate for theirthe atheroma's size such that the [[Caliber|calibre]] of the artery opening ([[Lumen (anatomy)|lumen]]) remains unchanged, until typically overabout 50% of the artery wall cross-sectional area consists of atheromatous tissue.<ref name=pmid3574413/>

[[File:Atheroma.jpg|thumb|302x302px|Narrowed arterial blood vessel blocked with an atheroma (artist's conception).]]

If the muscular wall enlargement eventually fails to keep up with the enlargement of the atheroma volume, or a clot forms and organizes over the plaque, then the [[Lumen (anatomy)|lumen]] of the artery becomes narrowed as a result of repeated ruptures, clots &and fibrosis over the tissues separating the atheroma from the blood stream. This narrowing becomes more common after decades of living, increasingly more common after people are in their 30s to 40s.{{cn|date=February 2021}}

The [[endothelium]] (the cell monolayer on the inside of the vessel) and covering tissue, termed [[fibrous cap]], separate atheroma from the blood in the [[Lumen (anatomy)|lumen]]. If a rupture (see [[vulnerable plaque]]) of the endothelium and fibrous cap occurs, then both a shower of debris from the plaque (debris larger than 5 micrometres are too large to pass through [[capillary|capillaries)]]) combined with a [[platelet]] and [[clotting]] response (an injury/repair response to both the debris and at the rupture site) begins within fractions of a second, eventually resulting in narrowing or sometimes closure of the [[Lumen (anatomy)|lumen]]. Eventually downstream tissue damage occurs due to closure or obstruction of downstream microvessels and/or closure of the lumen at the rupture, both resulting in loss of blood flow to downstream tissues. This is the principal mechanism of [[myocardial infarction]], [[stroke]] or other related [[cardiovascular disease]] problems.{{cn|date=February 2021}}

While clots at the rupture site typically shrink in volume over time, some of the clot may become organized into fibrotic tissue resulting in narrowing of the artery [[lumen (anatomy)|lumen]]; the narrowings sometimes seen on [[angiography]] examinations, if severe enough. Since angiography methods can only reveal larger lumens, typically larger than 200 micrometres, angiography after a cardiovascular event commonly does not reveal what happened.{{cn|date=February 2021}}

The accumulation (swelling) is always in the '''tunica intima''', between the [[endothelium]] lining and the smooth muscle [[tunica media|middle layer]] of the artery wall. {{cn|date=February 2021}}While the early stages, based on gross appearance, have traditionally been termed [[fatty streaks]] by pathologists, they are not composed of [[fat cells]] but of accumulations of [[white blood cells]], especially [[macrophages]], that have taken up oxidized [[low-density lipoprotein]] (LDL).{{cn|date=February 2021}}

[[Carotid]] [[Intima-media thickness]] Scan (CIMT can be measured by B-mode [[ultrasonography]]) measurement has been recommended by the [[American Heart Association]] as the most useful method to identify atherosclerosis and may now very well be the gold standard for detection.<ref>{{citationCite web needed|last=Poredos' |first='Pavel |title=Carotid intima-media thickness – indicator of cardiovascular risk |url=https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-1/Carotid-intima-media-thickness-indicator-of-cardiovascular-risk-Title-Carot,%20https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-1/Carotid-intima-media-thickness-indicator-of-cardiovascular-risk-Title-Carot |access-date=June2023-11-03 2014|website=www.escardio.org}}</ref>

Many approaches have been promoted{{by whom|date=June 2014}} as methods to reduce or reverse<ref name=":0">{{cite news |title=Ask the doctor: Reversing atherosclerosis? |url=https://www.health.harvard.edu/heart-health/ask-the-doctor-reversing-atherosclerosis |url-access=subscription|work=Harvard Health |date=November 2016 }}</ref> atheroma progression:{{citation needed|date=June 2014}}

* consuming foods containing [[omega-3omega−3]] fatty acids such as fish, fish-derived supplements, as well as flax seed oil, borage oil, and other non-animal-based oils;

* mouse studies indicated that subcutaneous administration of [[cyclodextrin|oligosaccharide 2-hydroxypropyl-βべーた-cyclodextrin]] (2HPβべーたCD) can solubilize [[cholesterol]], removing it from plaques.<ref>{{cite journal |last1=Zimmer |first1=Sebastian |last2=Grebe |first2=Alena |last3=Bakke |first3=Siril S. |last4=Bode |first4=Niklas |last5=Halvorsen |first5=Bente |last6=Ulas |first6=Thomas |last7=Skjelland |first7=Mona |last8=De Nardo |first8=Dominic |last9=Labzin |first9=Larisa I. |last10=Kerksiek |first10=Anja |last11=Hempel |first11=Chris |last12=Heneka |first12=Michael T. |last13=Hawxhurst |first13=Victoria |last14=Fitzgerald |first14=Michael L. |last15=Trebicka |first15=Jonel |last16=Björkhem |first16=Ingemar |last17=Gustafsson |first17=Jan-Åke |last18=Westerterp |first18=Marit |last19=Tall |first19=Alan R. |last20=Wright |first20=Samuel D. |last21=Espevik |first21=Terje |last22=Schultze |first22=Joachim L. |last23=Nickenig |first23=Georg |last24=Lütjohann |first24=Dieter |last25=Latz |first25=Eicke |title=Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming |journal=Science Translational Medicine |date=6 April 2016 |volume=8 |issue=333 |pages=333ra50 |doi=10.1126/scitranslmed.aad6100 |pmid=27053774 |pmc=4878149 }}</ref> However, later work concluded that "treatment with 2HPβべーたCD is ineffective in inducing atherosclerosis regression".<ref>{{Bettercite sourcejournal needed| last1=Snip | first1=Olga S.C. | last2=Hoekstra | first2=Menno | last3=Zhang | first3=Yiheng | last4=Geerling | first4=Janine J. | last5=Van Eck | first5=Miranda | title=2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice | journal=Biomolecules | publisher=MDPI AG | volume=12 | issue=9 | date=April31 August 2022 | issn=2218-273X | doi=10.3390/biom12091205 |url=https://www.mdpi.com/2218-273X/12/9/1205/pdf| page=1205| pmid=36139044 | pmc=9496214 | doi-access=free 2021}}</ref>

A significant proportion of artery flow-disrupting events occur at locations with less than 50% [[Lumen (anatomy)|lumenal]] narrowing. [[Cardiac stress test]]ing, traditionally the most commonly performed noninvasivenon-invasive testing method for blood flow limitations, generally only detects lumen narrowing ofgreater ~75%than orabout greater75%, although some physicians advocate [[nuclear stress methodstest]]s that can sometimes detect as little as 50%.{{Citation needed|date=August 2009}}

* {{cite journal |last1=Ornish |first1=Dean |last2=Scherwitz |first2=LW |last3=Billings |first3=JH |last4=Brown |first4=SE |last5=Gould |first5=KL |last6=Merritt |first6=TA |last7=Sparler |first7=S |last8=Armstrong |first8=WT |last9=Ports |first9=TA |last10=Kirkeeide |first10=RL |last11=Hogeboom |first11=C |last12=Brand |first12=RJ |title=Intensive Lifestyle Changes for Reversal of Coronary Heart Disease |journal=JAMA |date=16 December 1998 |volume=280 |issue=23 |pages=2001–7 |doi=10.1001/jama.280.23.2001 |pmid=9863851 |s2cid=21508600 }}

[[fr:Athérome]]<!-- This despite the redirection to [[fr:Athérosclérose]], because the French page currently have merged both article in one, but it will still works shall they be split again some day. -->