Dietary Neu5Ac Intervention Protects Against Atherosclerosis Associated With Human-Like Neu5Gc Loss-Brief Report
| Autor: | Kawanishi, Kunio, Coker, Joanna K, Grunddal, Kaare V, Dhar, Chirag, Hsiao, Jason, Zengler, Karsten, Varki, Nissi, Varki, Ajit, Gordts, Philip LSM |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Aging mice Pan troglodytes THP-1 Cells Knockout Clinical Sciences Aortic Diseases Cardiorespiratory Medicine and Haematology Inbred C57BL Cardiovascular Sialadenitis Antibodies Mixed Function Oxygenases LDL Mice Clinical Research Receptors Animals Humans Aorta Plaque Atherosclerotic Nutrition Animal Prevention mucins Atherosclerosis Animal Feed N-Acetylneuraminic Acid Diet High-Fat Cardiovascular System & Hematology inflammation Disease Models Dietary Supplements Neuraminic Acids N-acetylneuraminic acid atherosclerosis Foam Cells |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology, vol 41, iss 11 |
| Popis: | ObjectiveSpecies-specific pseudogenization of the CMAH gene during human evolution eliminated common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) biosynthesis from its precursor N-acetylneuraminic acid (Neu5Ac). With metabolic nonhuman Neu5Gc incorporation into endothelia from red meat, the major dietary source, anti-Neu5Gc antibodies appeared. Human-like Ldlr-/-Cmah-/- mice on a high-fat diet supplemented with a Neu5Gc-enriched mucin, to mimic human red meat consumption, suffered increased atherosclerosis if human-like anti-Neu5Gc antibodies were elicited.Approach and resultsWe now ask whether interventional Neu5Ac feeding attenuates metabolically incorporated Neu5Gc-mediated inflammatory acceleration of atherogenesis in this Cmah-/-Ldlr-/- model system. Switching to a Neu5Gc-free high-fat diet or adding a 5-fold excess of Collocalia mucoid-derived Neu5Ac in high-fat diet protects against accelerated atherosclerosis. Switching completely from a Neu5Gc-rich to a Neu5Ac-rich diet further reduces severity. Remarkably, feeding Neu5Ac-enriched high-fat diet alone has a substantial intrinsic protective effect against atherosclerosis in Ldlr-/- mice even in the absence of dietary Neu5Gc but only in the human-like Cmah-null background.ConclusionsInterventional Neu5Ac feeding can mitigate or prevent the red meat/Neu5Gc-mediated increased risk for atherosclerosis, and has an intrinsic protective effect, even in the absence of Neu5Gc feeding. These findings suggest that similar interventions should be tried in humans and that Neu5Ac-enriched diets alone should also be investigated further. |
| Databáze: | OpenAIRE |
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