Editing Low-density lipoprotein (section)

===Oxidized LDL===
Oxidized LDL (oxLDL) is a general term for LDL particles with oxidatively modified structural components. As a result, from [[free radical]] attack, both lipid and protein parts of LDL can be oxidized in the vascular wall. Besides the oxidative reactions in the vascular wall, oxidized lipids in LDL can also be derived from oxidized dietary lipids.<ref>{{Cite journal |last1=Staprans |first1=I. |last2=Rapp |first2=J. H. |last3=Pan |first3=X. M. |last4=Feingold |first4=K. R. |year=1996 |title=Oxidized lipids in the diet are incorporated by the liver into very low density lipoprotein in rats |journal=Journal of Lipid Research |volume=37 |issue=2 |pages=420–30 |doi=10.1016/S0022-2275(20)37628-8 |pmid=9026539 |doi-access=free}}</ref><ref name="Ahotupa">{{Cite journal |last=Ahotupa |first=Markku |year=2017 |title=Oxidized lipoprotein lipids and atherosclerosis |journal=Free Radical Research |volume=51 |issue=4 |pages=439–447 |doi=10.1080/10715762.2017.1319944 |pmid=28412863 |url=https://figshare.com/articles/journal_contribution/4986497 }}</ref> Oxidized LDL is known to associate with the development of [[atherosclerosis]], and it is therefore widely studied as a potential risk factor of [[cardiovascular diseases]].<ref name="Stocker">{{Cite journal |last1=Stocker |first1=Roland |last2=Keaney |first2=John F. |year=2004 |title=Role of Oxidative Modifications in Atherosclerosis |journal=Physiological Reviews |volume=84 |issue=4 |pages=1381–1478 |doi=10.1152/physrev.00047.2003 |pmid=15383655}}</ref> Atherogenicity of oxidized LDL has been explained by lack of recognition of oxidation-modified LDL structures by the LDL receptors, preventing the normal metabolism of LDL particles and leading eventually to the development of atherosclerotic plaques.<ref name=Stocker/> Of the lipid material contained in LDL, various lipid oxidation products are known as the ultimate atherogenic species.<ref>{{Cite journal |last=Birukov |first=K. G. |year=2006 |title=Oxidized lipids: The two faces of vascular inflammation |journal=Current Atherosclerosis Reports |volume=8 |issue=3 |pages=223–31 |doi=10.1007/s11883-006-0077-x |pmid=16640959 }}</ref> Acting as a transporter of these injurious molecules is another mechanism by which LDL can increase the risk of atherosclerosis.<ref name=Ahotupa/><ref>{{Cite journal |last1=Shao |first1=Baohai |last2=Heinecke |first2=Jay W. |year=2009 |title=HDL, lipid peroxidation, and atherosclerosis |journal=Journal of Lipid Research |volume=50 |issue=4 |pages=599–601 |doi=10.1194/jlr.E900001-JLR200 |pmc=2656652 |pmid=19141435 |doi-access=free}}</ref>

The [[LOX-1]] [[Scavenger receptor (immunology)|scavenge receptor]] does take up oxLDL, but the liver does not naturally express it.<ref>{{cite journal |last1=Wang |first1=Z |last2=Guo |first2=X |last3=Zhang |first3=Q |last4=Du |first4=G |last5=Zeng |first5=Z |last6=Zheng |first6=C |last7=Wei |first7=Y |title=Elimination of Ox-LDL through the liver inhibits advanced atherosclerotic plaque progression. |journal=International Journal of Medical Sciences |date=2021 |volume=18 |issue=16 |pages=3652–3664 |doi=10.7150/ijms.63065 |pmid=34790037|pmc=8579296 }}</ref> It is instead expressed by endothelial cells, platelets, macrophages, smooth muscle cells, and cardiomyocytes as an innate immune scavenge receptor. When activated, pro-inflammatory signals are generated in the cell, and damaging compounds are released as well. As a result, these cells are most sensitive to the effects of oxLDL.<ref>{{cite journal |last1=Barreto |first1=Joaquim |last2=Karathanasis |first2=Sotirios K. |last3=Remaley |first3=Alan |last4=Sposito |first4=Andrei C. |title=Role of LOX-1 (Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1) as a Cardiovascular Risk Predictor: Mechanistic Insight and Potential Clinical Use |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |date=January 2021 |volume=41 |issue=1 |pages=153–166 |doi=10.1161/ATVBAHA.120.315421|pmid=33176449 |pmc=9186447 }}</ref> [[SR-BI]] and [[CD36]], two class B scavenge receptors, also take up oxLDL into the macrophage.<ref>{{cite journal |last1=Sun |first1=B |last2=Boyanovsky |first2=BB |last3=Connelly |first3=MA |last4=Shridas |first4=P |last5=van der Westhuyzen |first5=DR |last6=Webb |first6=NR |title=Distinct mechanisms for OxLDL uptake and cellular trafficking by class B scavenger receptors CD36 and SR-BI. |journal=Journal of Lipid Research |date=December 2007 |volume=48 |issue=12 |pages=2560–70 |doi=10.1194/jlr.M700163-JLR200 |doi-access=free |pmid=17876058}}</ref>

Despite lower recognition efficacy by the LDLR, the liver does remove oxLDLs from the circulation. This is achieved by [[Kupffer cell]]s and [[liver sinusoidal endothelial cell]]s (LSECs). In LSECs, [[stabilin-1]] and [[stabilin-2]] mediate most of the uptake. Uptake of oxLDLs causes visible disruption to the structure of the LSEC in rats.<ref>{{cite journal |last1=Mao |first1=Hong |last2=Kruse |first2=Larissa D. |last3=Li |first3=Ruomei |last4=Oteiza |first4=Ana |last5=Struck |first5=Eike C. |last6=Schürstedt |first6=Jasmin |last7=Hübner |first7=Wolfgang |last8=Cogger |first8=Victoria C. |last9=Le Couteur |first9=David |last10=Wolfson |first10=Deanna L. |last11=Huser |first11=Thomas |last12=Ahluwalia |first12=Balpreet Singh |last13=Øie |first13=Cristina |last14=McCourt |first14=Peter A. G. |title=Impact of oxidized low-density lipoprotein on rat liver sinusoidal endothelial cell morphology and function |journal=npj Gut and Liver |date=23 October 2024 |volume=1 |issue=1 |doi=10.1038/s44355-024-00009-5|doi-access=free }}</ref> Doing the same also damages human LSEC cultures.<ref>{{cite journal |last1=Zhang |first1=Qi |last2=Liu |first2=Jing |last3=Liu |first3=Jia |last4=Huang |first4=Wenhui |last5=Tian |first5=Limin |last6=Quan |first6=Jinxing |last7=Wang |first7=Yunfang |last8=Niu |first8=Ruilan |title=oxLDL induces injury and defenestration of human liver sinusoidal endothelial cells via LOX1 |journal=Journal of Molecular Endocrinology |date=October 2014 |volume=53 |issue=2 |pages=281–293 |doi=10.1530/JME-14-0049|pmid=25057109 }}</ref>