Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation
| Autor: | Abd Alla, Joshua, Jamous, Yahya F, Quitterer, Ursula |
|---|---|
| Přispěvatelé: | University of Zurich, Quitterer, Ursula |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
1503 Catalysis
QH301-705.5 AGTR1 10050 Institute of Pharmacology and Toxicology 1607 Spectroscopy heart failure 610 Medicine & health Cardiomegaly transgenic mice angiotensin II lipid overload Receptor Angiotensin Type 1 Article Mice 1312 Molecular Biology 1706 Computer Science Applications Animals Humans Biology (General) QD1-999 cardiac dysfunction 1604 Inorganic Chemistry AT1 receptor Lipid Metabolism SCD Chemistry Disease Models Animal Gene Expression Regulation Scd1 Cardiac dysfunction 570 Life sciences biology Tumor Suppressor Protein p53 1606 Physical and Theoretical Chemistry Stearoyl-CoA Desaturase 1605 Organic Chemistry |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 18 International Journal of Molecular Sciences, Vol 22, Iss 9883, p 9883 (2021) International Journal of Molecular Sciences, 22 (18) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22189883 |
| Popis: | Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and/or volume overload. Because the pathophysiological role of Scd1/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 ± 2.9% compared to 54.3 ± 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein. International Journal of Molecular Sciences, 22 (18) ISSN:1422-0067 |
| Databáze: | OpenAIRE |
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