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The clearance of these remnant lipoproteins involves binding to heparin sulfate proteoglycans and the LDLR like protein -1 (LRP1) in the hepatic space of Disse, in a process called secretion capture that requires local enrichment by hepatic expression of apoE The Cholesterol Hypothesis Studies by Anitschkow showing that feeding cholesterol in oil to rabbits caused the formation of atheroma, similar to those seen in humans, demonstrated a causal role of cholesterol in the pathogenesis of atherosclerosis in 1913 (220)

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Critically, arginine scarcity triggers a pathological shift in NOS activity, from NO production to superoxide (O 2 - ) and reactive nitrogen oxide species (RNOS) generation, which amplifies T-cell suppression through combined oxidative damage and signal blockade (192, 193)