• Oxysterols like 7-ketocholesterol and 25-hydroxycholesterol are found in oxidized LDL (oxLDL).
• Promote:
  • Foam cell formation
  • Endothelial dysfunction
  • Inflammation in arterial walls

Implication: Major contributors to plaque development and coronary artery disease.

Mutations in enzymes that process oxysterols can cause severe syndromes.

• Cerebrotendinous xanthomatosis (CTX): Defect in CYP27A1 → accumulation of 27-hydroxycholesterol
• Smith-Lemli-Opitz Syndrome: Accumulation of toxic cholesterol precursors
• Niemann-Pick type C: Oxysterols used as diagnostic biomarkers

Oxysterols can cross the blood-brain barrier and affect neuronal health.

• 24(S)-hydroxycholesterol: Involved in brain cholesterol turnover
  • Altered in Alzheimer’s disease
• 27-hydroxycholesterol: Linked to cognitive decline
  • May promote amyloid-beta deposition and tau pathology

Associated Conditions:

• Alzheimer’s disease
• Parkinson’s disease
• Multiple sclerosis

Some oxysterols can promote or inhibit tumorigenesis depending on context.

• 27-hydroxycholesterol acts as a selective estrogen receptor modulator (SERM)
  • Promotes ER-positive breast cancer growth
• Oxysterols may also influence:
  • Tumor immune evasion
  • Angiogenesis
  • Metastasis

• 25-hydroxycholesterol: Involved in innate immunity
  • Regulates interferon response
  • Can have antiviral activity
• Chronic elevation may contribute to autoimmunity or inflammation