التفاصيل البيبلوغرافية
| العنوان: |
Implication of Sphingolipid Metabolism Gene Dysregulation and Cardiac Sphingosine-1-Phosphate Accumulation in Heart Failure |
| المؤلفون: |
Lorena Pérez-Carrillo, Isaac Giménez-Escamilla, Luis Martínez-Dolz, Ignacio José Sánchez-Lázaro, Manuel Portolés, Esther Roselló-Lletí, Estefanía Tarazón |
| المصدر: |
Biomedicines; Volume 10; Issue 1; Pages: 135 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2022 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
heart failure, sphingolipid metabolism, sphingosine-1-phosphate (S1P), ceramide synthase 1 ( CERS1 ), ceramide/S1P rheostat |
| الوصف: |
Disturbances in sphingolipid metabolism lead to biological function dysregulation in many diseases, but it has not been described in heart failure (HF). Sphingosine-1-phosphate (S1P) levels have not ever been measured in the myocardium. Therefore, we analyze the gene dysregulation of human cardiac tissue by mRNA-seq (n = 36) and ncRNA-seq (n = 50). We observed most major changes in the expression of genes belonging to de novo and salvage pathways, and the tight gene regulation by their miRNAs is largely dysregulated in HF. We verified using ELISA (n = 41) that ceramide and S1P accumulate in HF cardiac tissue, with an increase in the ceramide/S1P ratio of 57% in HF. Additionally, changes in left ventricular mass and diameters are directly related to CERS1 expression and inversely related to S1P levels. Altogether, we define changes in the main components of the sphingolipid metabolism pathways in HF, mainly de novo and salvage, which lead to an increase in ceramide and S1P in cardiac tissue, as well as an increase in the ceramide/S1P ratio in HF patients. Therapeutic gene modulation focused on restoring ceramide levels or reversing the ceramide/S1P ratio could be a potential therapy to be explored for HF patients. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Molecular Genetics and Genetic Diseases; https://dx.doi.org/10.3390/biomedicines10010135Test |
| DOI: |
10.3390/biomedicines10010135 |
| الإتاحة: |
https://doi.org/10.3390/biomedicines10010135Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.9959357F |
| قاعدة البيانات: |
BASE |
