Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations
Mutant desmoglein 2 (DSG2) is the second most common pathogenic gene in arrhythmogenic cardiomyopathy (ACM), accounting for approximately 10% of ACM cases. In addition to common clinical and pathological features, ACM caused by mutant DSG2 has specific characteristics, manifesting as left ventricle...
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| Format: | Article |
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Elsevier
2023-11-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223012465 |
| _version_ | 1797660591306833920 |
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| author | Baowei Zhang Yizhang Wu Xingbo Yang Yaozu Xiang Bing Yang |
| author_facet | Baowei Zhang Yizhang Wu Xingbo Yang Yaozu Xiang Bing Yang |
| author_sort | Baowei Zhang |
| collection | DOAJ |
| description | Mutant desmoglein 2 (DSG2) is the second most common pathogenic gene in arrhythmogenic cardiomyopathy (ACM), accounting for approximately 10% of ACM cases. In addition to common clinical and pathological features, ACM caused by mutant DSG2 has specific characteristics, manifesting as left ventricle involvement and a high risk of heart failure. Pathological studies have shown extensive cardiomyocyte necrosis, infiltration of immune cells, and fibrofatty replacement in both ventricles, as well as abnormal desmosome structures in the hearts of humans and mice with mutant DSG2-related ACM. Although desmosome dysfunction is a common pathway in the pathogenesis of mutant DSG2-related ACM, the mechanisms underlying this dysfunction vary among mutations. Desmosome dysfunction induces cardiomyocyte injury, plakoglobin dislocation, and gap junction dysfunction, all of which contribute to the initiation and progression of ACM. Additionally, dysregulated inflammation, overactivation of transforming growth factor-beta-1 signaling and endoplasmic reticulum stress, and cardiac metabolic dysfunction contribute to the pathogenesis of ACM caused by mutant DSG2. These features demonstrate that patients with mutant DSG2-related ACM should be managed individually and precisely based on the genotype and phenotype. Further studies are needed to investigate the underlying mechanisms and to identify novel therapies to reverse or attenuate the progression of ACM caused by mutant DSG2. |
| first_indexed | 2024-03-11T18:32:07Z |
| format | Article |
| id | doaj.art-911fb148d47a4ea792acb03e788e9f37 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T18:32:07Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-911fb148d47a4ea792acb03e788e9f372023-10-13T11:02:39ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-11-01167115448Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutationsBaowei Zhang0Yizhang Wu1Xingbo Yang2Yaozu Xiang3Bing Yang4Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong, Shanghai 200120, PR ChinaDepartment of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong, Shanghai 200120, PR ChinaShanghai East Hospital, School of Life Sciences and Technology, Tongji University, 150 Jimo Road, Pudong, Shanghai 200120, PR ChinaShanghai East Hospital, School of Life Sciences and Technology, Tongji University, 150 Jimo Road, Pudong, Shanghai 200120, PR China; Corresponding author.Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong, Shanghai 200120, PR China; Correspondence to: Arrhythmia Diagnosis and Treatment Center, Shanghai East Hospital, Tongji University, 150 Jimo Road, Pudong, Shanghai 200120, PR China.Mutant desmoglein 2 (DSG2) is the second most common pathogenic gene in arrhythmogenic cardiomyopathy (ACM), accounting for approximately 10% of ACM cases. In addition to common clinical and pathological features, ACM caused by mutant DSG2 has specific characteristics, manifesting as left ventricle involvement and a high risk of heart failure. Pathological studies have shown extensive cardiomyocyte necrosis, infiltration of immune cells, and fibrofatty replacement in both ventricles, as well as abnormal desmosome structures in the hearts of humans and mice with mutant DSG2-related ACM. Although desmosome dysfunction is a common pathway in the pathogenesis of mutant DSG2-related ACM, the mechanisms underlying this dysfunction vary among mutations. Desmosome dysfunction induces cardiomyocyte injury, plakoglobin dislocation, and gap junction dysfunction, all of which contribute to the initiation and progression of ACM. Additionally, dysregulated inflammation, overactivation of transforming growth factor-beta-1 signaling and endoplasmic reticulum stress, and cardiac metabolic dysfunction contribute to the pathogenesis of ACM caused by mutant DSG2. These features demonstrate that patients with mutant DSG2-related ACM should be managed individually and precisely based on the genotype and phenotype. Further studies are needed to investigate the underlying mechanisms and to identify novel therapies to reverse or attenuate the progression of ACM caused by mutant DSG2.http://www.sciencedirect.com/science/article/pii/S0753332223012465Arrhythmogenic cardiomyopathyDesmoglein 2Desmosome dysfunctionInflammationCardiac fibrosis |
| spellingShingle | Baowei Zhang Yizhang Wu Xingbo Yang Yaozu Xiang Bing Yang Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations Biomedicine & Pharmacotherapy Arrhythmogenic cardiomyopathy Desmoglein 2 Desmosome dysfunction Inflammation Cardiac fibrosis |
| title | Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations |
| title_full | Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations |
| title_fullStr | Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations |
| title_full_unstemmed | Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations |
| title_short | Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations |
| title_sort | molecular insight into arrhythmogenic cardiomyopathy caused by dsg2 mutations |
| topic | Arrhythmogenic cardiomyopathy Desmoglein 2 Desmosome dysfunction Inflammation Cardiac fibrosis |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223012465 |
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