{
  "id": 10480528,
  "title": "Aggregated Low-Density Lipoprotein (agLDL) Triggers Inflammatory Responses in Macrophages through Toll-Like Receptor 4 (TLR4)",
  "url": "https://urgent.news/2026/09/28/aggregated-low-density-lipoprotein-agldl-triggers-inflammatory",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754244v1?rss=1"
  },
  "original_language": "en",
  "account": "Atherosclerosis, a chronic inflammatory disease, begins with low-density lipoproteins (LDL) accumulating and modifying under the endothelial layer. Although oxidized LDL (oxLDL) is known to exist in such lesions, aggregated LDL (agLDL) is also prevalent. Aggregated LDL is considered a substrate for macrophages to engulf and form foam cells.\n\nRecent research reveals that agLDL, via toll-like receptor 4 (TLR4), triggers macrophages to create lysosomal synapses that facilitate its degradation, a process called digestive exophagy. As TLR4 is a pattern-recognition receptor for inflammation in macrophages, it was hypothesized that agLDL could initiate inflammation in macrophages alongside lipoprotein degradation.\n\nThis study confirms that agLDL directly activates the canonical NF-{kappa}B signaling pathway, triggering a pro-inflammatory transcriptional response through TLR4. The activation of TLR4 by agLDL resembles the response to classical lipopolysaccharide (LPS). Moreover, agLDL activates TLR4, leading to the formation of inflammatory macrophages that recruit immune cells, a critical step in atherosclerotic lesion development.\n\nThese findings establish a novel dual role for agLDL: it serves as both a lipid donor and an inflammatory stimulus. This connection between LDL aggregation in the arterial wall and the initiation of sterile vascular inflammation offers new insights into the role of digestive exophagy, highlighting its mechanistic significance.",
  "summary": "Atherosclerosis is a chronic inflammatory disease primarily initiated by the sub-endothelial retention and modification of low-density lipoproteins (LDL), such as oxidation and aggregation. While oxidized LDL (oxLDL) exists in atherosclerotic lesions, aggregated lipoproteins are also prominent. Aggregated LDL (agLDL), for instance, is viewed as a passive substrate for macrophages to uptake and…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}