Impaired cholesterol and LDL uptake pathways in the development of oncological and cardiovascular diseases
Por:
Curco, AS, Garcia, E, Polishchuk, A, La chica-Lhoest, MT, Llorente-Cortes, V
Publicada:
1 nov 2025
Ahead of Print:
1 sep 2025
Resumen:
Dietary lipids play a critical role in the development of cardiovascular disease and cancer by influencing key cellular processes. Lipoprotein and fatty acid receptors activate intracellular signaling pathways that promote tumor growth and vascular remodeling. A key event in both cancer and vascular diseases is the retention of lowdensity lipoproteins (LDL) and other lipoprotein particles by proteoglycans in the extracellular matrix (ECM) of atherosclerotic plaques and the tumor stroma. This retention facilitates lipoprotein modification processes. Dysregulated uptake of modified lipoproteins-particularly through receptors that are not downregulated by intracellular cholesterol levels-leads to excessive lipid accumulation within lipid droplets (LDs) and other intracellular organelles. The lipid and protein content of LDs and mitochondria determine the biophysical and functional characteristics of the crucial interactions between these suborgalles. In particular, lipid-derived mediators such as prostaglandins, leukotrienes, ceramides, oxidized fatty acids, and cholesterol can disrupt LD biogenesis and dynamics, impair mitochondrial function, and alter the expression, activity, and subcellular localization of proteins that regulate LD-mitochondria interactions. Dysfunctional communication between LDs and mitochondria contributes to the onset and progression of cancer and cardiovascular disease by disturbing cellular metabolism and energy homeostasis. Common LDL-related mechanisms in atherosclerosis and cancer have been summarized in Figure 1.
Filiaciones:
Curco, AS:
Inst Biomed Res Barcelona IIBB, Spanish Natl Res Council CSIC, Barcelona, Spain
Inst Recerca St Pau IR SANT PAU, Barcelona 08041, Spain
Garcia, E:
Inst Biomed Res Barcelona IIBB, Spanish Natl Res Council CSIC, Barcelona, Spain
Inst Recerca St Pau IR SANT PAU, Barcelona 08041, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona 08041, Spain
Polishchuk, A:
Inst Biomed Res Barcelona IIBB, Spanish Natl Res Council CSIC, Barcelona, Spain
Inst Recerca St Pau IR SANT PAU, Barcelona 08041, Spain
La chica-Lhoest, MT:
Inst Biomed Res Barcelona IIBB, Spanish Natl Res Council CSIC, Barcelona, Spain
Inst Recerca St Pau IR SANT PAU, Barcelona 08041, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Barcelona 08041, Spain
Llorente-Cortes, V:
Inst Biomed Res Barcelona IIBB, Spanish Natl Res Council CSIC, Barcelona, Spain
Inst Recerca St Pau IR SANT PAU, Barcelona 08041, Spain
Inst Hlth Carlos III, CIBERCV, Madrid 28029, Spain
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