
-   LOX-1 triggers apoptosis via internalization of Ox-LDL, which induces Bcl-2- associated X protein (Bax)/Bcl-2 pathway activation via increasing Bax/Bcl-2 ratio by down-regulation of Bcl-1 or through activation of the proapoptotic agents caspase-3/caspase-9 pathway in vascular smooth muscle cells [PMID: 11397703]. Additionally, Ox-LDL can induce apoptosis in other types of cells as coronary artery endothelial cells and macrophages [PMID: 21338316].
-   LOX-1/Ox-LDL complex stimulates p38 MAPK signal pathway that promotes matrix metalloprotease (MMP) expression and activity inducing collagen formation and fibrosis [PMID: 15485683].
-   Human liver sinusoidal endothelial cells HLSECs cultured with high glucose medium exhibited increased LOX-1 mRNA expression and reduced autophagy. Silencing of LOX-1 reversed these effects, indicating the involvement of the LOX-1-mediated AMPK/HNF4alpha signaling pathway in autophagy regulation in HLSECs under high glucose conditions [PMID: 36590506]. Treatment of HLSECs with oxLDL significantly increased LOX1 mRNA and protein expression in a dose- and time-dependent manner. This upregulation was linked to increased ROS generation, NF-kappaB activation, altered ET1 and caveolin 1 levels, and eNOS downregulation, leading to reduced fenestra diameter and porosity in HLSECs [PMID: 25057109].
-   Human L02 hepatoma cells treated with palmitate showed increased LOX-1 expression and ER stress; this was mitigated by DHA treatment and siRNA-mediated LOX-1 knockdown, while LOX-1 overexpression intensified ER stress [PMID: 32853678].
-   Tunicamycin-induced endoplasmic reticulum stress in hepatic L02 cells resulted in the downregulation of LOX-1 mRNA expression and reduced lipid uptake. High-density lipoprotein (HDL) treatment mitigated these effects, maintaining LOX-1 expression and lipid uptake levels by inhibiting the IRE1/XBP-1 pathway [PMID: 25923692].

## Summary

Olr1 encodes the LOX-1 receptor, which functions in the recognition and removal of oxidatively modified low-density lipoprotein (oxLDL) from the bloodstream, which is a protective function intended to reduce lipid accumulation and consequent cellular damage [CS: 9]. This protective action is essential in the context of kidney stresses, where increased glycation end-products and toxic lipid derivative accumulation typically occur in conditions such as diabetes mellitus, ischemia-reperfusion injury, and chronic renal failure [CS: 8]. The elevation of LOX-1 serves as an acute response to clear these harmful substances, thus safeguarding the endothelial cells and maintaining kidney function [CS: 8].

Upon encountering stress stimuli like oxidative stress, inflammation, or hypertensive conditions, LOX-1 expression is elevated [CS: 9]. Enhanced LOX-1 expression acts to internalize and degrade the accumulating oxLDL within the kidney, aiming to neutralize the threat of lipid peroxidation and endothelial dysfunction [CS: 8]. However, this protective mechanism when perpetually engaged can inadvertently lead to a prolonged inflammatory state with increased ROS production and NF-kappa-B activation [CS: 8].
