دورية أكاديمية
Oxidized LDL‐dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy
| العنوان: | Oxidized LDL‐dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy |
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| المؤلفون: | Elena Sommariva, Ilaria Stadiotti, Michela Casella, Valentina Catto, Antonio Dello Russo, Corrado Carbucicchio, Lorenzo Arnaboldi, Simona De Metrio, Giuseppina Milano, Alessandro Scopece, Manuel Casaburo, Daniele Andreini, Saima Mushtaq, Edoardo Conte, Mattia Chiesa, Walter Birchmeier, Elisa Cogliati, Adolfo Paolin, Eva König, Viviana Meraviglia, Monica De Musso, Chiara Volani, Giada Cattelan, Werner Rauhe, Linda Turnu, Benedetta Porro, Matteo Pedrazzini, Marina Camera, Alberto Corsini, Claudio Tondo, Alessandra Rossini, Giulio Pompilio |
| المصدر: | EMBO Molecular Medicine, Vol 13, Iss 9, Pp n/a-n/a (2021) |
| بيانات النشر: | Springer Nature, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | Arrhythmogenic Cardiomyopathy, ARVC, adipogenesis, oxidative stress, lipoproteins, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro‐adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low‐density lipoprotein (oxLDL)‐dependent activation of PPARγ, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient‐derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARγ upregulation. By boosting oxLDL in a Pkp2 heterozygous knock‐out mice through high‐fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.202114365 |
| URL الوصول: | https://doaj.org/article/301c35b9793845e3942738060fda5380 |
| رقم الأكسشن: | edsdoj.301c35b9793845e3942738060fda5380 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.202114365 |