{
  "abstract": "Background: Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cerebrovascular disease, but its effects on the cerebral microcirculation are poorly defined. We investigated whether LDL-C is associated with pericyte dysfunction in acute ischemic stroke (AIS) and explored underlying mechanisms. Methods: Serum soluble platelet-derived growth factor receptor-{beta} (sPDGFR{beta}) was measured in two independent AIS cohorts (n=97 and n=86). Cerebral pericyte transcriptional responses to LDL-C were analyzed by single-cell RNA sequencing in Apoe-knockout mice fed control or high-fat diet (n=4 [male/female: 2/2]/group), and cultured human brain pericytes were exposed to purified human LDL cholesterol with or without N-acetyl-L-cysteine. Results: Higher serum sPDGFR{beta} was associated with greater neurological deficit and circulating neurofilament light chain. LDL-C positively correlated with sPDGFR{beta} in both clinical cohorts. High-fat diet induced coordinated suppression of type-I interferon pathways, and a positive shift in reactive oxygen species-related transcriptional programs in mouse pericytes; exploratory sex-by-diet analyses suggested larger transcriptional responses in females. In cultured human pericytes, LDL-C induced oxidative-stress, lipid-handling, and ferroptosis-associated transcriptional programs while suppressing type-I interferon signaling. Cross-species enrichment analysis showed that LDL-C-induced and -repressed signatures in cultured pericytes aligned with the sex-by-diet interaction in Apoe-knockout mice. LDL-C also reduced cell-surface PDGFR{beta} and increased sPDGFR{beta} release in cultured pericytes, which were significantly attenuated by N-acetyl-L-cysteine, whereas LDH activity increased numerically but not significantly. Conclusions: Clinical and experimental findings support an LDL-pericyte axis linking atherogenic lipid stress to cerebral microvascular dysfunction, with possible sex-dependent modulation of oxidative stress and type-I interferon signaling as potential mechanisms.",
  "abstract_shown": true,
  "affiliations": [
    "Saarland University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "F. Wang"
    },
    {
      "name": "W. Quan"
    },
    {
      "name": "G. Wu"
    },
    {
      "name": "J. Yang"
    },
    {
      "name": "X. Wang"
    },
    {
      "name": "Q. Cao"
    },
    {
      "name": "W. Hao"
    },
    {
      "name": "E. Wang"
    },
    {
      "name": "T. Furihata"
    },
    {
      "name": "W. Xu"
    },
    {
      "name": "D. Li"
    },
    {
      "name": "S. Ke"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6vym2nkkgr14n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.27.754749",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754749v1.full",
  "id": "6vym2nkkgr14n",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754749v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7216328259",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754749v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6vym2nkkgr14n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:49Z",
      "native_id": "10.64898/2026.09.27.754749",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754749v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Low-Density Lipoprotein Cholesterol and Cerebral Pericyte Dysfunction in Acute Ischemic Stroke: Clinical and Experimental Evidence",
  "title_text": "Low-Density Lipoprotein Cholesterol and Cerebral Pericyte Dysfunction in Acute Ischemic Stroke: Clinical and Experimental Evidence",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:49Z",
  "url": "https://research.draconitic.com/paper/6vym2nkkgr14n",
  "venue": "bioRxiv",
  "versions": []
}