Sialic acid content of human low density lipoproteins affects their
interaction with cell receptors and intracellular lipid accumulation.
Low density lipoproteins (LDL) isolated from the plasma of patients with angiographically demonstrable coronary heart disease (CHD) induced accumulation of triglycerides, free cholesterol, and cholesteryl esters in cultured macrophages, smooth muscle cells, and endothelial cells derived from uninvolved intima of human aorta, but not in skin fibroblasts or hepatoma cells. The sialic acid content of LDL from CHD patients was 40-75% lower than that from healthy donors. There was a negative correlation between LDL sialic acid content and the LDL-induced accumulation of total intracellular cholesterol. Neuraminidase treatment of LDL from normal healthy donors produced sialic acid-depleted LDL (Ds-LDL) which was able to stimulate intracellular lipid accumulation. Neuraminidase treatment of LDL from CHD patients further increased its capacity to induce intracellular lipid accumulation. Sialic acid-poor LDL isolated by affinity chromatography of LDL from CHD patients induced a 2- to 4-fold increase of free and esterified cholesterol in human intimal smooth muscle cells. Binding, uptake, and degradation of 125I-labeled Ds-LDL by macrophages and endothelial cells were 1.5- to 2-fold higher than for native LDL. Binding and uptake of Ds-LDL was inhibited 64-93% by the addition of 20-fold excess acetylated LDL (Ac-LDL); in the inverse experiment, the level of inhibition was 35-54%. These data indicate that a sialic acid-poor form of LDL isolated from CHD patients can interact with both native and scavenger LDL receptors. A sialic acid-poor form of LDL may be a naturally occurring ligand that interacts with the scavenger receptor(s) on macrophages and endothelial cells.
Peter at Hyperlipid has gone into this subject, I'm having trouble finding the link. This study was in a list of studies related to a study he posted about sialic acid lack on the other side of the equation, in lesions in the artery wall, leading to the delivery of fat and cholesterol to the wound area.
So what depletes the sialic acid?
Thus, in the blood of over 95% of the CHD patients examined, we found a modified, sialic acid-poor form of LDL that determines the potential of a patient's plasma to cause lipid accumulation in arterial cells. Additional evidence indicating the presence of sialic acid-depleted LDL in the blood of CHD patients has recently been obtained. In these patients, we have found anti-LDL autoantibodies with much greater affinity for sialic acid depleted LDL than for native LDL or chemically modified LDL (28). This observation strongly suggests that desialylation is a significant LDL modification that occurs in vivo.
A vegan blogger might use this to peg red meat as the cause of heart disease. I am not a vegan blogger.
Most mammals make a type of sialic acid called Neu5gc. Humans can only make a precursor of Neu5gc called Neu5AC. Sialic acid is used as a marker-molecule in the immune system. The body develops anti-bodies to the Neu5GC.
Humans are weird. We don't make vitamin c; important to collagen formation. We don't make allantoin; which is oxidized from uric acid, (I'll post about that sometime) which is also important to collagen formation, both are important to healing, including broken arteries. One more weirdness; we don't make Neu5Gc, instead we have an immune reaction to it. Could all three of these be related?
The Neu5gc concentration is very low in most human tissue. The few places where it is high, the fetus, tumours, the gut-- are also the tissues with the most growth or turnover. So, if our mother eats red meat, we have lots of Neu5gc initially, but over time general maintenance weeds that out and replaces it with the stuff we make ourselves, the Neu5Ac.
A vegan blogger might tell you the Neu5gc finds its way into the tumour because meat causes cancer. I'm not going to tell you that. Maybe red meat also causes babies and intestines. But there are implications of that Neu5gc. If you're fighting cancer, for instance, cancer cells conveniently tagged with foreign sialic acid might come in handy to the immune response, especially if doctors find a way to take advantage of this.
Now, here's the question;
Is there something about Neu5Ac that makes it more prone to the degradation of its sialic acid? That isn't the question I thought I was going to ask. I'll go ahead and ask that question anyways; Is there something about the Neu5Gc that makes it prone to the degradation of its sialic acid? Or is there something about it that changes it's general distribution?
Given the known differences in sialic acid biology between humans and great apes (Varki 2008), we also stained normal-appearing myocardial sections from humans
and apes with two lectins that bind sialic acids: Sambucus nigra agglutinin (SNA) which recognizes terminal Siaa2-6Galb1-4GlcNAcb- units on N-linked glycan chains of glycoproteins, and Maackia Amurensis hemagglutinin (MAH), which recognizes Siaa2-3Gal termini on various glycoconjugates (Martin et al. 2002; Varki and Varki 2007). Both SNA and MAH strongly stained large areas of heart sections from chimpanzees, gorillas and orangutans, with MAH staining again showing evidence of encircling ‘bundles’ that were not seen in human heart sections (Fig. 4). These differences with SNA and MAH lectin staining imply that terminal sialic acids are much denser in the great ape heart.
Varki should maybe read Hyperlipid. He (Varki) seems to think the purpose of the healing process in chimpanzees and in humans is to kill the subject. Chimpanzees and humans don't heal the same. So although both get heart disease, which is basically a mis-healing, it looks different.
Paraffin sections of hearts from humans, chimpanzees, gorillas, and orangutans were stained using the Masson-Trichrome stain for collagen. As shown in Fig. 3, otherwise normal heart sections from all three great apes showed collagen bundles that appeared to divide the heart muscle along the planes where the larger blood vessels were situated. This pattern was not observed in the human heart sections.
Okay. Another anomaly; missing collagen bundles. Humans are collagen-challenged. We can't make vitamin c or allantoin (not on purpose. uric acid can still oxidize into allantoin, but we lack the specific enzyme.)
Just in case I didn't actually say what I meant to say, here it is; unable to make vitamin c or allantoin on purpose, our collagen making ability is compromised. We need to somehow live in spite of this; something about our metabolism of sialic acid causes our damaged arteries to use material and energy from ldl cholesterol for repair. This keeps us from being dead.