Familial dilated cardiomyopathy: A multidisciplinary entity, from basic screening to novel circulating biomarkers

Gonzalo-Calvo, David de; Quezada, Maribel; Campuzano, Òscar; Pérez‐Serra, Alexandra; Broncano, Jordi; Ayala, R.; Ramos, Mónica; Llorente‐Cortés, Vicenta; Blasco-Turrión, Sara; Morales, Francisco J.; González, Pablo; Brugada, Ramón; Mangas, Alipio; Toro, Rocío

doi:10.1016/j.ijcard.2016.11.045

Cited by 23 publications

(12 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…***P Ͻ 0.001. loading conditions and severe coronary disease (9,10). It has also been characterized by remodeling of the LV, causing loss of normal ventricular geometry, leading to impaired function (6). The morphological and functional alterations observed in MrgD KO mice are in line with these characteristics.…”

Section: Discussionmentioning

confidence: 93%

Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice

Oliveira

Melo

Motta‐Santos

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

We have recently described a new peptide of the renin-angiotensin system, alamandine, a derivative of angiotensin-(1–7). Mas-related G protein-coupled receptor member D (MrgD) was identified as its receptor. Although similar cardioprotective effects of alamandine to those of angiotensin-(1–7) have been described, the significance of this peptide in heart function is still elusive. We aimed to evaluate the functional role of the alamandine receptor MrgD in the heart using MrgD-deficient mice. MrgD was localized in cardiomyocytes by immunofluorescence using confocal microscopy. High-resolution echocardiography was performed in wild-type and MrgD-deficient mice (2 and 12 wk old) under isoflurane anesthesia. Standard B-mode images were obtained in the right and left parasternal long and short axes for morphological and functional assessment and evaluation of cardiac deformation. Additional heart function evaluation was performed using Langendorff isolated heart preparations and inotropic measurements of isolated cardiomyocytes. Immunofluorescence indicated that the MrgD receptor is expressed in cardiomyocytes, mainly in the membrane and perinuclear and nuclear regions. Echocardiography showed left ventricular remodeling and severe dysfunction in MrgD-deficient mice. Strikingly, MrgD-deficient mice presented a pronounced dilated cardiomyopathy with a marked decrease in systolic function. Echocardiographic changes were supported by the data obtained in isolated hearts and inotropic measurements in cardiomyocytes. Our data add new evidence for a major role for alamandine/MrgD in the heart. Furthermore, our results indicate that we have identified a new gene implicated in dilated cardiomyopathy, unveiling a new target for translational approaches aimed to treat heart diseases. NEW & NOTEWORTHY The renin-angiotensin system is a key target for cardiovascular therapy. We have recently identified a new vasodepressor/cardioprotective angiotensin, alamandine. Here, we unmasked a key role for its receptor, Mas-related G protein-coupled receptor member D (MrgD), in heart function. The severe dilated cardiomyopathy observed in MrgD-deficient mice warrants clinical and preclinical studies to unveil its potential use in cardiovascular therapy. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/mrgd-deficiency-leads-to-dilated-cardiomyopathy/ .

show abstract

Section: Discussionmentioning

confidence: 93%

Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice

Oliveira

Melo

Motta‐Santos

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Many health professionals should be involved, including cardiologists, radiologists and geneticists. 7 Nonetheless, overlapping phenotypes often make differential diagnosis unclear. This situation represents a major challenge in the cardiology arena.…”

Section: Dilated Cardiomyopathy: a Heterogeneous Entity Encompassing mentioning

confidence: 99%

Emerging role of microRNAs in dilated cardiomyopathy: evidence regarding etiology

Calderón‐Domínguez

Belmonte

Quezada-Feijoó

et al. 2020

Translational Research

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease. This cardiac disorder is a major health problem due to its high prevalence, morbidity, and mortality. DCM is a complex disease with a common phenotype but heterogeneous pathological mechanisms. Early etiological diagnosis and prognosis stratification is crucial for the clinical management of the patient. Advances in imaging technology and genetic tests have provided useful tools for clinical practice. Nevertheless, the assessment of the disease remains challenging. Novel noninvasive indicators are still needed to assist in decisionmaking. microRNAs (miRNAs), a group of small noncoding RNAs, have been identified as key mediators of cell biology. They are found in a stable form in body fluids and their concentration is altered in response to stress. Previous research has suggested that the miRNA signature constitutes a novel source of noninvasive biomarkers for a wide array of cardiovascular diseases. Specifically, several studies have reported the potential role of miRNAs as clinical indicators among the etiologies of DCM. However, this field has not been reviewed in detail. Here, we summarize the evidence of intracellular and circulating miRNAs in DCM and their usefulness in the development of novel diagnostic, prognostic and therapeutic approaches, with a focus on DCM etiology. Although the findings are still

show abstract

“…34 Dilated Cardiomyopathy DCM is often defined as left ventricular dilatation together with systolic dysfunction; up to 40-50% of DCM cases could have a genetic variant identified in one of the 60 genes currently associated with the condition. 35 It was previously suggested that each of the multiple genes known to be associated with the condition contributed <5% of the cases, until the discovery of TTN-related DCM in the genomic era, which could account for up to 20% of cases. 36 Truncating variants in TTN, the largest gene in humans with alternate splicing, have been associated with DCM, yet are also identified in a normal control population.…”

Section: Arrhythmogenic Cardiomyopathymentioning

confidence: 99%

Practical Aspects in Genetic Testing for Cardiomyopathies and Channelopathies

Lee

Ching

2019

CBR

View full text Add to dashboard Cite

Genetic testing has an increasingly important role in the diagnosis and management of cardiac disorders, where it confirms the diagnosis, aids prognostication and risk stratification and guides treatment. A genetic diagnosis in the proband also enables clarification of the risk for family members by cascade testing. Genetics in cardiac disorders is complex where epigenetic and environmental factors might come into interplay. Incomplete penetrance and variable expressivity is also common. Genetic results in cardiac conditions are mostly probabilistic and should be interpreted with all available clinical information. With this complexity in cardiac genetics, testing is only indicated in patients with a strong suspicion of an inheritable cardiac disorder after a full clinical evaluation. In this review we discuss the genetics underlying the major cardiomyopathies and channelopathies, and the practical aspects of diagnosing these conditions in the laboratory.

show abstract

Familial dilated cardiomyopathy: A multidisciplinary entity, from basic screening to novel circulating biomarkers

Cited by 23 publications

References 126 publications

Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice

Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice

Emerging role of microRNAs in dilated cardiomyopathy: evidence regarding etiology

Practical Aspects in Genetic Testing for Cardiomyopathies and Channelopathies

Contact Info

Product

Resources

About