SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1
The CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascert...
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MDPI AG
2021-01-01
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| author | Shuyu Piao Ikjun Lee Seon-Ah Jin Seonhee Kim Harsha Nagar Su-jeong Choi Byeong Hwa Jeon Cuk-Seong Kim |
| author_facet | Shuyu Piao Ikjun Lee Seon-Ah Jin Seonhee Kim Harsha Nagar Su-jeong Choi Byeong Hwa Jeon Cuk-Seong Kim |
| author_sort | Shuyu Piao |
| collection | DOAJ |
| description | The CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascertain whether dysfunctional endothelial CRIF1 influences cardiac function and is mediated by the antioxidant protein sirtuin 1 (SIRT1). We also examined the effect of the potent SIRT1 activator SRT1720 on cardiac dysfunction. Mice with endothelial cell-specific CRIF1 deletion showed an increased heart-to-body weight ratio, increased lethality, and markedly reduced fractional shortening of the left ventricle, resulting in severe cardiac dysfunction. Moreover, endothelial cell-specific CRIF1 deletion resulted in mitochondrial dysfunction, reduced ATP levels, inflammation, and excessive oxidative stress in heart tissues, associated with decreased SIRT1 expression. Intraperitoneal injection of SRT1720 ameliorated cardiac dysfunction by activating endothelial nitric oxide synthase, reducing oxidative stress, and inhibiting inflammation. Furthermore, the decreased endothelial junction-associated protein zonula occludens-1 in CRIF1-deleted mice was significantly recovered after SRT1720 treatment. Our results suggest that endothelial CRIF1 plays an important role in maintaining cardiac function, and that SIRT1 induction could be a therapeutic strategy for endothelial dysfunction-induced cardiac dysfunction. |
| first_indexed | 2024-03-09T05:32:54Z |
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| language | English |
| last_indexed | 2024-03-09T05:32:54Z |
| publishDate | 2021-01-01 |
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| spelling | doaj.art-11191558e0f448c88e21ff5553e300ec2023-12-03T12:31:06ZengMDPI AGBiomedicines2227-90592021-01-01915210.3390/biomedicines9010052SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1Shuyu Piao0Ikjun Lee1Seon-Ah Jin2Seonhee Kim3Harsha Nagar4Su-jeong Choi5Byeong Hwa Jeon6Cuk-Seong Kim7Department of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaDepartment of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaDivision of Cardiology, School of Medicine, Chungnam National University Hospital, Daejeon 301-747, KoreaDepartment of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaDepartment of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaDepartment of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaDepartment of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaDepartment of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, KoreaThe CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascertain whether dysfunctional endothelial CRIF1 influences cardiac function and is mediated by the antioxidant protein sirtuin 1 (SIRT1). We also examined the effect of the potent SIRT1 activator SRT1720 on cardiac dysfunction. Mice with endothelial cell-specific CRIF1 deletion showed an increased heart-to-body weight ratio, increased lethality, and markedly reduced fractional shortening of the left ventricle, resulting in severe cardiac dysfunction. Moreover, endothelial cell-specific CRIF1 deletion resulted in mitochondrial dysfunction, reduced ATP levels, inflammation, and excessive oxidative stress in heart tissues, associated with decreased SIRT1 expression. Intraperitoneal injection of SRT1720 ameliorated cardiac dysfunction by activating endothelial nitric oxide synthase, reducing oxidative stress, and inhibiting inflammation. Furthermore, the decreased endothelial junction-associated protein zonula occludens-1 in CRIF1-deleted mice was significantly recovered after SRT1720 treatment. Our results suggest that endothelial CRIF1 plays an important role in maintaining cardiac function, and that SIRT1 induction could be a therapeutic strategy for endothelial dysfunction-induced cardiac dysfunction.https://www.mdpi.com/2227-9059/9/1/52CRIF1 proteinendothelial cellscardiomyocytessirtuin 1 |
| spellingShingle | Shuyu Piao Ikjun Lee Seon-Ah Jin Seonhee Kim Harsha Nagar Su-jeong Choi Byeong Hwa Jeon Cuk-Seong Kim SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1 Biomedicines CRIF1 protein endothelial cells cardiomyocytes sirtuin 1 |
| title | SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1 |
| title_full | SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1 |
| title_fullStr | SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1 |
| title_full_unstemmed | SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1 |
| title_short | SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1 |
| title_sort | sirt1 activation attenuates the cardiac dysfunction induced by endothelial cell specific deletion of crif1 |
| topic | CRIF1 protein endothelial cells cardiomyocytes sirtuin 1 |
| url | https://www.mdpi.com/2227-9059/9/1/52 |
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