Not many people know that the LDL particles which are floating around in our body play an active role in our immune system. I know of the gram-negative bacteria being captured because their endotoxin, lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) via HDL particles (a good reason to have high HDL) and then transfers it on to LDL to get cleared via the liver.
“Lipopolysaccharide Is Transferred from High-Density to Low-Density Lipoproteins by Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087464/
“Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865154/
I recently bumped against this Twitter tread. It adds to the knowledge above and because it is a good summary, I didn’t want to let it go lost in the volatile world of tweets. So I’ve taken it as it is so that me or anyone else can dive into it in more detail if they want to.
Staphylococcus aureus alpha-toxin is bound, and almost totally inactivated, in vitro by LDL.
“Binding and partial inactivation of Staphylococcus aureus alpha-toxin by human plasma low density lipoprotein” ; https://www.jbc.org/article/S0021-9258(20)81980-2/pdf ; https://pubmed.ncbi.nlm.nih.gov/6853557/
LDL can bind to pH6-Ag, a potential adhesive for the bacterial pathogen Yersinia pestis.
“pH6 antigen of Yersinia pestis interacts with plasma lipoproteins and cell membranes” https://pubmed.ncbi.nlm.nih.gov/12576514/ ; https://www.jlr.org/article/S0022-2275(20)31219-0/fulltext
Rats injected with mortal bacterial toxins survive if they are injected with human LDL.
“Infections May be Causal in the Pathogenesis of Atherosclerosis” https://www.amjmedsci.org/article/S0002-9629(15)30809-0/fulltext
LDL can also bind to certain viruses.
“SA-11 rotavirus binding to human serum lipoproteins” https://link.springer.com/article/10.1007/BF00189426
In a meta-analysis of 19 cohort studies including almost 70,000 deaths, it was found an inverse association between serum cholesterol and mortality from respiratory and gastrointestinal diseases, most of which are of an infectious origin.
“High cholesterol may protect against infections and atherosclerosis” https://academic.oup.com/qjmed/article/96/12/927/1533176?login=false
In another study of more than 100 000 individuals followed for 15 years, a strong, inverse association was found between total cholesterol and the risk of being admitted to hospital because of pneumonia or influenza.
“Serum total cholesterol and risk of hospitalization, and death from respiratory disease” https://pubmed.ncbi.nlm.nih.gov/9447398/ ; https://academic.oup.com/ije/article/26/6/1191/676876?login=false
A study of 2446 unmarried men with a previous hx of sexually transmitted disease or liver disease followed for 14 years, a risk ratio for HIV infection of 1.66 was shown in the lowest cholesterol quartile compared with the risk in the second quartile.
“Association between serum total cholesterol and HIV infection in a high-risk cohort of young men” https://pubmed.ncbi.nlm.nih.gov/9436759/ ; https://journals.lww.com/jaids/Abstract/1998/01010/Association_Between_Serum_Total_Cholesterol_and.8.aspx
Very low total cholesterol is seen in Smith-Lemli-Opitz syndrome, due to imperfect function of an enzyme involved in cholesterol synthesis. Many children with this syndrome are stillborn or die and those who survive have frequent and severe infections.
“High cholesterol may protect against infections and atherosclerosis” https://academic.oup.com/qjmed/article/96/12/927/1533176?login=false
Individuals with familial hypercholesterolemia (FH) have very high LDL-C and t-C due to LDL-receptor deficiency. In one study three carriers of a mutation for FH were identified through screening. Their standardized mortality ratio was lower than normal.
The authors concluded that environmental factors may participate in the causation of coronary heart disease in FH, and that hypercholesterolemia may have conferred a survival advantage when infectious disease was prevalent.
“Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study” https://pubmed.ncbi.nlm.nih.gov/11325764/ ; https://www.bmj.com/content/322/7293/1019
Certain inflammatory conditions are associated with increased LDL-C.
“Regulation of low-density lipoprotein cholesterol by intestinal inflammation and the acute phase response” https://academic.oup.com/cardiovascres/article/114/2/226/4682789?login=false
Problems arise when inflammation turns chronic. Increase in small dense LDL and Lipoprotein(a) occurs in inflammatory diseases but not infections (both atherogenic) L(a) is a LDL variant containing a protein called apolipoprotein(a).
“The Effect of Inflammation and Infection on Lipids and Lipoproteins” https://www.ncbi.nlm.nih.gov/books/NBK326741/
Platelet-activating factor (PAF) is a potent phospholipid mediator that was first described by its ability to cause platelet aggregation and dilation of blood vessels. Under normal conditions, plasma and tissue levels of PAF are tightly regulated by its metabolic pathways.
“However, production of PAF and PAF-like molecules can become elevated and/or dysregulated during extended periods of immune activation and chronic inflammation-related disorders”
“If unresolved, the PAF cycle-related inflammatory activation of endothelial cells leads to tight adhesion of leukocytes on the activated endothelium and subsequent migration of these leukocytes and Ox-LDL to the subendothelium.”
“Inflammation, not Cholesterol, Is a Cause of Chronic Disease” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986484/
Oxidized low-density lipoprotein (Ox-LDL) is involved in atherogenesis.
Inflammation matters. Melatonin likely helps.
“Melatonin Attenuates ox-LDL-Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling” https://pubmed.ncbi.nlm.nih.gov/33763168/ ; https://www.hindawi.com/journals/omcl/2021/5589612/
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