Impaired cholesterol and LDL uptake pathways in the development of oncological and cardiovascular diseases
García Rodríguez, Jesús Eduardo (Institut de Recerca Sant Pau)
Polishchuk, Anna (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Llorente-Cortés, Vicenta (Institut de Recerca Sant Pau)
Solanelles Curco, Angels (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
La Chica Lhoëst, María Teresa (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2025
Resum:	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 low-density 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.
Ajuts:	2021/SGR-00834 Instituto de Salud Carlos III PI21/01523
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Matèria:	Cardiovascular ; Diet ; Fatty acids ; Lipid droplets ; Lipoprotein receptors ; Lipoproteins ; Mitochondria ; Tumor
Publicat a:	Seminars in Cancer Biology, Vol. 116 (November 2025) , p. 84-95, ISSN 1096-3650

DOI: 10.1016/j.semcancer.2025.09.004
PMID: 40998097

12 p, 4.1 MB

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