Abstract:
:Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management.
journal_name
Circ Resjournal_title
Circulation researchauthors
McNally EM,Mestroni Ldoi
10.1161/CIRCRESAHA.116.309396subject
Has Abstractpub_date
2017-09-15 00:00:00pages
731-748issue
7eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.309396journal_volume
121pub_type
杂志文章,评审abstract::Obesity results in marked alterations in cardiac energy metabolism, with a prominent effect being an increase in fatty acid uptake and oxidation by the heart. Obesity also results in dramatic changes in the release of adipokines, such as leptin and adiponectin, both of which have emerged as important regulators of car...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.107.150417
更新日期:2007-08-17 00:00:00
abstract::The proteoglycan versican is implicated in several atherogenic events, including stimulation of vascular smooth muscle cell (VSMC) growth and migration, retention of lipoproteins, and promotion of thrombogenesis. A high content of intimal versican also correlates with a low content of elastin, suggesting an inhibitory...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000202051.28319.c8
更新日期:2006-02-17 00:00:00
abstract:RATIONALE:We have recently shown that the bone morphogenetic protein (BMP) antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. Our initial studies discovered that Grem2 is strongly induced in the adult heart after experimental myocardial infarction (MI). However, th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308700
更新日期:2016-07-22 00:00:00
abstract:RATIONALE:Increased sympathetic nerve activity has been linked to the pathogenesis of hypertension in humans and animal models. Enhanced peripheral chemoreceptor sensitivity which increases sympathetic nerve activity has been observed in established hypertension but has not been identified as a possible mechanism for i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206946
更新日期:2010-02-19 00:00:00
abstract::Cyclic GMP modulates gene expression in vascular smooth muscle cells (SMCs) in part by stimulating cGMP-dependent protein kinase I (PKGI) and the phosphorylation of transcription factors. In some cells, cGMP increases nuclear translocation of PKGI and PKGI-dependent phosphorylation of transcription regulators; however...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.176321
更新日期:2008-07-03 00:00:00
abstract::Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000081594.21764.44
更新日期:2003-07-25 00:00:00
abstract::Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes, macrophages, and dendritic cells. A decade ago, studies on macrophage behavior in atherosclerotic lesions were often limited to quantification of total macrophage area in cross-sections of plaques. Although technological advances are still nee...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.114.301174
更新日期:2014-05-23 00:00:00
abstract::Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.114.302721
更新日期:2014-06-06 00:00:00
abstract:RATIONALE:The sarcolemma of cardiomyocytes contains many proteins that are essential for electromechanical function in general, and excitation-contraction coupling in particular. The distribution of these proteins is nonuniform between the bulk sarcolemmal surface and membrane invaginations known as transverse tubules ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317266
更新日期:2021-01-22 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.156901
更新日期:2007-07-20 00:00:00
abstract::Adenosine, a vasodilator metabolite, is often produced in tissues where the demand for oxygen exceeds the supply. We have recently demonstrated in isolated cannulated arterioles that adenosine and its metabolite, inosine, can also cause vasoconstriction by stimulation of mast cells. Secondary release of histamine and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.627
更新日期:1996-04-01 00:00:00
abstract::Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made dis...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.4.470
更新日期:1980-04-01 00:00:00
abstract::Increasing evidence indicates that the control of cell proliferation and apoptosis are linked. The c-myc proto-oncogene is induced early after cell-cycle entry in vascular smooth muscle cells (VSMCs) in vitro and after arterial injury and regulates both cell proliferation and apoptosis. Although both proliferation and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.7.820
更新日期:1999-04-16 00:00:00
abstract:RATIONALE:Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. OBJECTIVE:The goal of this study was to assess whether genome editing using a clus...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304351
更新日期:2014-08-15 00:00:00
abstract::Calcineurin, a calcium/calmodulin-regulated protein phosphatase, modulates gene expression in cardiac and skeletal muscles during development and in remodeling responses such as cardiac hypertrophy that are evoked by environmental stresses or disease. Recently, we identified two genes encoding proteins (MCIP1 and MCIP...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.12.e61
更新日期:2000-12-08 00:00:00
abstract::Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accura...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/RES.0000000000000110
更新日期:2016-08-19 00:00:00
abstract::Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emerg...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000109792.43271.47
更新日期:2004-02-06 00:00:00
abstract::We discuss the recent finding by Mizishima's group regarding the role of the autophagy-related conjugation system in mediating the closure of autophagosomes and its implication in the study of autophagy in mammalian cells. The study not only shows a novel function of the autophagy-related conjugation system but also i...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.117.310450
更新日期:2017-02-17 00:00:00
abstract::Angiotensin (Ang) II is present inside vascular smooth muscle cells (VSMCs); however, its intracellular functions, if any, are unknown. We tested the hypothesis that intracellular Ang II exerts effects on cytosolic Ca2+ ([Ca2+]i) in VSMCs. Ang II was administered via microinjection. Intracellular Ang II localization w...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.4.765
更新日期:1996-10-01 00:00:00
abstract::The purpose of this study was to explore the changes in fetal blood volume that occur after fetal hemorrhage. Fifteen unanesthetized, chronically catheterized fetal sheep averaging 130 +/- 3 (SD) days gestation were studied 4 to 6 (average 5) days after catheter implantation. The fetuses were hemorrhaged by continuous...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.6.730
更新日期:1983-06-01 00:00:00
abstract::Ventricular repolarization was analyzed by measuring epicardial potential distributions in intact dogs with single or multiple ectopic foci and a minimum at the terminal site(s) of excitation. During the latter half of the T wave the distributions became more complex, and two maxima evolved from the initial one at eac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.4.475
更新日期:1976-10-01 00:00:00
abstract::The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.2.231
更新日期:1985-02-01 00:00:00
abstract:RATIONALE:Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies ha...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.270132
更新日期:2012-09-28 00:00:00
abstract::Atherosclerotic plaque rupture is the main cause of coronary thrombosis and myocardial infarcts. Currently, there is no animal model of plaque disruption. We have developed a rabbit model in which an atherosclerotic plaque can be ruptured at will after an inflatable balloon becomes embedded into the plaque. Furthermor...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.7.705
更新日期:1998-10-05 00:00:00
abstract::It is believed that inotropic agents exert their effects in cardiac muscle via a modulation of Ca2+ cycling; however, the involvement of phospholipase activation and the biochemical pathways participating in inotropic responsiveness remain unclear. The aim of the current study was to determine whether arachidonic acid...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.2.376
更新日期:1993-02-01 00:00:00
abstract::Electrical uncoupling at gap junctions during acute myocardial ischemia contributes to conduction abnormalities and reentrant arrhythmias. Increased levels of intracellular Ca(2+) and H(+) and accumulation of amphipathic lipid metabolites during ischemia promote uncoupling, but other mechanisms may play a role. We tes...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.8.656
更新日期:2000-10-13 00:00:00
abstract::The E-cadherin/beta-catenin/T-cell factor (Tcf) signaling pathway plays a crucial role in embryogenesis and carcinogenesis and has recently emerged in atherosclerosis. The aim of this work was to investigate whether this signaling pathway is involved in smooth muscle cell proliferation induced by oxidized low-density ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.166405
更新日期:2008-09-26 00:00:00
abstract::Mechanical overload elicits functional and structural adaptive mechanisms in cardiac muscle. Signaling pathways linked to integrin/cytoskeleton complexes may have a function in mediation of the effects of mechanical stimulus in myocardial cells. We investigated the tyrosine phosphorylation and the assembly of the mult...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.7.558
更新日期:2000-09-29 00:00:00
abstract::We studied alpha- and beta-adrenoceptor-mediated responses of rabbit facial vein rings to adrenergic stimulation to determine the location of the two types of receptors in relation to the sympathetic nerve terminals. Transmural electrical nerve stimulation (TNS) at low frequency elicited large beta-receptor-mediated r...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.2.486
更新日期:1981-08-01 00:00:00
abstract::5-Hydroxytryptamine (5-HT)(1B) receptors mediate contraction in human pulmonary arteries, and 5-HT(1B) receptor-mediated contraction is enhanced in pulmonary arteries from hypoxic rats. Here we further examine the role of this receptor in the development of pulmonary hypertension (PHT) by examining (1) the effects of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2401.100426
更新日期:2001-12-07 00:00:00