Advances in the Genetic Basis and Pathogenesis of Sarcomere Cardiomyopathies.
Annu Rev Genomics Hum Genet
; 20: 129-153, 2019 08 31.
Article
em En
| MEDLINE
| ID: mdl-30978303
ABSTRACT
Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are common heart muscle disorders that are caused by pathogenic variants in sarcomere protein genes. HCM is characterized by unexplained cardiac hypertrophy (increased chamber wall thickness) that is accompanied by enhanced cardiac contractility and impaired relaxation. DCM is defined as increased ventricular chamber volume with contractile impairment. In this review, we discuss recent analyses that provide new insights into the molecular mechanisms that cause these conditions. HCM studies have uncovered the critical importance of conformational changes that occur during relaxation and enable energy conservation, which are frequently disturbed by HCM mutations. DCM studies have demonstrated the considerable prevalence of truncating variants in titin and have discerned that these variants reduce contractile function by impairing sarcomerogenesis. These new pathophysiologic mechanisms open exciting opportunities to identify new pharmacological targets and develop future cardioprotective strategies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcômeros
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Cardiomiopatia Hipertrófica
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Cardiomiopatia Dilatada
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Conectina
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Contração Miocárdica
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article