Figure 1: LDL and oxLDL particles bind to their respective receptors on hepatocytes, facilitating their endosomal uptake and elimination. PCSK9 binding to the receptors promotes lysosomal degradation, rather than recycling to the cell surface, making the receptors unavailable for LDL and oxLDL scavenging. Microbial products (e.g. lipopolysaccharide on Gram negative bacterial surfaces) or cell debris bind LRP1 receptor facilitating pathogen clearance and inhibiting the inflammatory response. PCSK9 binding to LRP1 promotes lysosomal degradation of the receptor, thus making the receptor unavailable for pathogen scavenging. Like LDL-R, LRP1 also binds circulating lipoproteins. In macrophages, CD36 functions as a co-factor for TLRs inducing a pro-inflammatory response to ox-LDL. Abbreviations: LDL-R: low density lipoprotein receptor; oxLDL: oxidized LDL; PCSK9: proprotein convertase subtilisin/kexin 9; LRP-1: LDL receptor related protein 1; TLR: Toll-like receptor.