Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients
Puig Grifol, Núria (Institut de Recerca Sant Pau)
Rives, José (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Gil-Millan, Pedro (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Miñambres, Inka (Institut de Recerca Sant Pau)
Ginel, Antonino (Institut de Recerca Sant Pau)
Tauron, Manel (Institut de Recerca Sant Pau)
Bonaterra-Pastra, Anna (Hospital Universitari Vall d'Hebron)
Hernandez Guillamon, Maria Mar (Hospital Universitari Vall d'Hebron)
Pérez Pérez, Antonio (Institut de Recerca Sant Pau)
Sanchez-Quesada, Jose Luis (Institut de Recerca Sant Pau)
Benitez, Sonia (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Diabetic patients present increased volume and functional alterations in epicardial adipose tissue (EAT). We aimed to analyze EAT from type 2 diabetic patients and the inflammatory and cytotoxic effects induced on cardiomyocytes. Furthermore, we analyzed the cardioprotective role of apolipoprotein J (apoJ). EAT explants were obtained from nondiabetic patients (ND), diabetic patients without coronary disease (DM), and DM patients with coronary disease (DM-C) after heart surgery. Morphological characteristics and gene expression were evaluated. Explants were cultured for 24 h and the content of nonesterified fatty acids (NEFA) and sphingolipid species in secretomes was evaluated by lipidomic analysis. Afterwards, secretomes were added to AC16 human cardiomyocytes for 24 h in the presence or absence of cardioprotective molecules (apoJ and HDL). Cytokine release and apoptosis/necrosis were assessed by ELISA and flow cytometry. The EAT from the diabetic samples showed altered expression of genes related to lipid accumulation, insulin resistance, and inflammation. The secretomes from the DM samples presented an increased ratio of pro/antiatherogenic ceramide (Cer) species, while those from DM-C contained the highest concentration of saturated NEFA. DM and DM-C secretomes promoted inflammation and cytotoxicity on AC16 cardiomyocytes. Exogenous Cer16:0, Cer24:1, and palmitic acid reproduced deleterious effects in AC16 cells. These effects were attenuated by exogenous apoJ. Diabetic secretomes promoted inflammation and cytotoxicity in cardiomyocytes. This effect was exacerbated in the secretomes of the DM-C samples. The increased content of specific NEFA and ceramide species seems to play a key role in inducing such deleterious effects, which are attenuated by apoJ.
Ajuts:	Ministerio de Economía y Competitividad PI16/00471 Instituto de Salud Carlos III PI20/00334 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1149
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Apolipoprotein J ; Apoptosis ; Ceramides ; Coronary artery disease ; Epicardial adipose tissue ; Fatty acids ; Inflammation ; Type 2 diabetes
Publicat a:	Biomedicine & pharmacotherapy, Vol. 175 (june 2024) , p. 116779, ISSN 1950-6007

DOI: 10.1016/j.biopha.2024.116779
PMID: 38776681

13 p, 1.0 MB

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