par Bondue, Antoine ;Arbustini, Eloisa;Bianco, Anna M;Ciccarelli, Michele;Dawson, Dana;De Rosa, Matteo;Hamdani, Nazha;Hilfiker-Kleiner, Denise;Meder, Benjamin;Leite-Moreira, Adelino;Thum, Thomas;Tocchetti, Carlo C.G.;Varricchi, Gilda;Van Der Velden, Jolanda;Walsh, Roddy;Heymans, Stephane
Référence Cardiovascular Research, 114, 10, page (1287-1303)
Publication Publié, 2018-08
Référence Cardiovascular Research, 114, 10, page (1287-1303)
Publication Publié, 2018-08
Article révisé par les pairs
Résumé : | Dilated cardiomyopathy (DCM) frequently affects relatively young, economically, and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance-malignancy of the mutated gene-but also on epigenetics, age, toxic factors, pregnancy, and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart. |