Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
Actis Dato, Virginia (Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI))
Paz, María C. (Consejo Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI))
Rey, Federico E. (University of Wisconsin-Madison)
Sánchez, María C. (Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI))
Llorente-Cortés, Vicenta (Institut d'Investigació Biomèdica Sant Pau)
Chiabrando, Gustavo A. (Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC))
Ceschin, Danilo G. (Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC))
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	Cardiovascular disease (CVD) is a multisystemic and multicellular pathology that is generally associated with high levels of atherogenic lipoproteins in circulation. These lipoproteins tend to be retained and modified, for example, aggregated low-density lipoprotein (aggLDL), in the extracellular matrix of different tissues, such as the vascular wall and heart. The uptake of aggLDL generates a significant increase in cholesteryl ester (CE) in these tissues. We previously found that the accumulation of CE generates alterations in the insulin response in the heart. Although the insulin response is mainly associated with the uptake and metabolism of glucose, other studies have shown that insulin would fulfill functions in this tissue, such as regulating the calcium cycle and cardiac contractility. Here, we found that aggLDL induced-lipid accumulation altered the gene expression profile involved in processes essential for cardiac functionality, including insulin response and glucose uptake (Insr, Ins1, Pik3ip1, Slc2a4 gene expression), calcium cycle (Cacna1s and Gjc2 gene expression) and calcium-dependent cardiac contractility (Myh3), and cholesterol efflux (Abca1), in HL-1 cardiomyocytes. These observations were recapitulated using an in vivo model of hypercholesterolemic ApoE-KO mice. Altogether, these results may explain the deleterious effect of lipid accumulation in the myocardium, with important implications for lipid-overloaded associated CVD, including impaired insulin response, disrupted lipid metabolism, altered cardiac structure, and increased susceptibility to cardiovascular events.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Scientific reports, Vol. 13 Núm. 1 (december 2023) , p. 8761, ISSN 2045-2322

DOI: 10.1038/s41598-023-35951-6
PMID: 37253991

11 p, 4.0 MB

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