Dilated cardiomyopathy

Schultheiss, Heinz‐Peter; Fairweather, DeLisa; Caforio, Alida L.P.; Escher, Felicitas; Hershberger, Ray E.; Lipshultz, Steven E.; Liu, Peter P.; Matsumori, Akira; Mazzanti, Andrea; McMurray, John J.V.; Priori, Silvia G.

doi:10.1038/s41572-019-0084-1

Cited by 478 publications

(470 citation statements)

References 262 publications

(270 reference statements)

Supporting

Mentioning

437

Contrasting

Unclassified

Order By: Relevance

“…Mutations in Nexn are associated with cardiomyopathy, especially for the DCM, and result in dilated ventricular chambers and impaired contraction 28,31 . Myocardial damage will finally lead to refractory heart failure and fatal arrhythmia 36 . Compared with WT, a significantly increased EDV and ESV, and decreased EF, could be observed in the Het animals.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of real‐time cardiac MRI in mice using tiny golden angle radial sparse

Metze

Abaei

et al. 2020

NMR in Biomedicine

View full text Add to dashboard Cite

Cardiovascular magnetic resonance imaging has proven valuable for the assessment of structural and functional cardiac abnormalities. Even although it is an established imaging method in small animals, the long acquisition times of gated or self-gated techniques still limit its widespread application. In this study, the application of tiny golden angle radial sparse MRI (tyGRASP) for real-time cardiac imaging was tested in 12 constitutive nexilin (Nexn) knock-out (KO) mice, both heterozygous (Het, N = 6) and wild-type (WT, N = 6), and the resulting functional parameters were compared with a well-established self-gating approach. Real-time images were reconstructed for different temporal resolutions of between 16.8 and 79.8 ms per image. The suggested approach was additionally tested for dobutamine stress and qualitative first-pass perfusion imaging. Measurements were repeated twice within 2 weeks for reproducibility assessment. In direct comparison with the high-quality, self-gated technique, the real-time approach did not show any significant differences in global function parameters for acquisition times below 50 ms (rest) and 31.5 ms (stress).Compared with WT, the end-diastolic volume (EDV) and end-systolic volume (ESV) were markedly higher (P < 0.05) and the ejection fraction (EF) was significantly lower in the Het Nexn-KO mice at rest (P < 0.001). For the stress investigation, a clear decrease of EDV and ESV, and an increase in EF, but maintained stroke volume, could be observed in both groups. Combined with ECG-triggering, tyGRASP provided firstpass perfusion data with a temporal resolution of one image per heartbeat, allowing the quantitative assessment of upslope curves in the blood-pool and myocardium.Excellent inter-study reproducibility was achieved in all the functional parameters.The tyGRASP is a valuable real-time MRI technique for mice, which significantly reduces the scan time in preclinical cardiac functional imaging, providing sufficient image quality for deriving accurate functional parameters, and has the potential to investigate real-time and beat-to-beat changes.

show abstract

Section: Discussionmentioning

confidence: 99%

Feasibility of real‐time cardiac MRI in mice using tiny golden angle radial sparse

Metze

Abaei

et al. 2020

NMR in Biomedicine

View full text Add to dashboard Cite

show abstract

“…However, those with an exuberant immune response can manifest acute myocarditis with heart failure or cardiogenic shock, accompanied by hypercytokinemia and inflammatory cell infiltration of the heart 40 . With support the patients can recover, but some persist with inflammatory cardiomyopathy 41 . In a parallel with the SARS infection, in which lymphopenia was also observed to be highly prognostic, reports showed an early reduction in T cells, in particular a reduction in CD4+ more than CD8+ T cells 44 with SARS-CoV in senescent mice.…”

Section: Virus-receptor and The Immune System Interactionsmentioning

confidence: 99%

The Science Underlying COVID-19

et al. 2020

Self Cite

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.

show abstract

“…DCM is a non-ischaemic cardiac muscle disease with structural and functional myocardial malformations. Gene mutation can induce DCM, including genes encoding structural elements of the sarcomere and desmosome [2]. In the present study, we obtained the DCM gene data from the GSE19303 dataset using the bioinformatics analysis method and identi ed 538 genes that might involve in this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Dilated cardiomyopathy (DCM) is a non-ischaemic cardiac muscle disease with structural and functional myocardial aberration by the presence of left ventricular ectasia and contractile dysfunction [1][2][3]. The WHO de nes DCM as serious cardiac disarray that can lead to extensive morbidity and mortality just that complications in particular heart failure and arrhythmia [4].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Quan¹,

Miao²

2020

Preprint

View full text Add to dashboard Cite

Background: Dilated cardiomyopathy (DCM) is a non-ischaemic cardiac muscle disease with structural and functional myocardial aberration can lead to extensive morbidity and mortality due to complications in particular heart failure and arrhythmia. Two classic Chinese medicine formulas, Shenfu decoction and Linguizhugan decoction, were both shown to exert therapeutic effects on heart disease. Thus, modified Shenfu and Linguizhugan decoction (SFLGZGD) is recommended for treatment DCM. However, its chemical and pharmacological characteristics remain to be elucidated. In the current study, a network pharmacology approach was applied to characterize the action mechanism and target genes of SFLGZGD on DCM.Methods: The gene expression of DCM was obtained from the Gene Expression Omnibus (GEO). All compounds were obtained from the correlative databases, and active mixture were selected according to their oral bioavailability (OB) and drug-likeness (DL) index. The potential targets of SFLGZGD were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database. The compound-target and target-pathway networks were constructed. The protein-protein interactive (PPI) network generated by R software was visualized by Cytoscape, and the topology scores, functional regions, and gene annotations were analyzed using plugins of Bisogenet and CytoNCA. The potential pathways related to target genes were determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.Results: A total of 963 differentially expressed genes (DEGs), including 538 upregulated genes and 425 downregulated, were obtained from GSE19303. A total of 636 ingredients in SFLGZGD were obtained, among which, 93 were chosen as bioactive components. The compound-target network included 10 bioactive components and 18 potential targets and a total of 1939 genes obtained in the PPI network, among them, a total of 16 genes were screened out. Moreover,129 terms on the GO analysis and six pathways obtained. Among these potential targets, EGFR, CDKN1A, MMP1, COL1A1, COL3A1, MMP3, ICAM1, and HSPB1 were identified as relatively high-degree targets.Conclusions: The network pharmacology-based approach in the current study has shown promising potential in identifying major therapeutic targets from TCM formulations. Besides, our study suggested that network pharmacology prediction may provide a useful tool for describing the molecular mechanism of SFLGZGD on DCM.

show abstract

Dilated cardiomyopathy

Cited by 478 publications

References 262 publications

Feasibility of real‐time cardiac MRI in mice using tiny golden angle radial sparse

Feasibility of real‐time cardiac MRI in mice using tiny golden angle radial sparse

The Science Underlying COVID-19

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Contact Info

Product

Resources

About