Loss of embryonic neural crest cardiomyocytes causes adult hypertrophic cardiomyopathy

AbstractNeural crest cells migrate to the embryonic heart and transform into a small number of cardiomyocytes, but their functions in the developing and adult heart are unknown. Here, we map the fates of neural crest derived cardiomyocytes (NC-Cms) and genetically ablate them in embryogenesis in zebrafish. Specific NC-Cm ablation results in aberrant trabeculation patterns and altered Notch signaling, but is not detrimental to the development of the fish or early heart function. Strikingly, embryonic NC-Cm ablation results in adult fish that show severely hypertrabeculated hearts, altered cardiomyocyte size, diminished adult heart capacity and consequently poor physiological response to cardiac stress tests. Thus, we identify a novel developmental mechanism and genetic pathway that predisposes adults to hypertrophic cardiomyopathy and provides the first zebrafish model of adult-onset heart failure.

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Neural Crest Derived Cardiomyocytes Regulate Cardiac Trabeculation and Adult Heart Function.

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.18.3 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Sarah Abdul‐Wajid ◽

Bradley Demarest ◽

H Joseph Yost

Keyword(s):

Neural Crest ◽

Heart Function ◽

Adult Heart

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Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish

Nature Communications ◽

10.1038/s41467-018-07054-8 ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 16

Author(s):

Sarah Abdul-Wajid ◽

Bradley L. Demarest ◽

H. Joseph Yost

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Neural Crest ◽

Adult Onset

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Guidelines and Implications for Selecting Preoperative Cardiac Stress Tests

The Journal for Nurse Practitioners ◽

10.1016/j.nurpra.2017.06.021 ◽

2017 ◽

Vol 13 (8) ◽

pp. 505-511 ◽

Cited By ~ 1

Author(s):

Joan E. King

Keyword(s):

Stress Tests ◽

Cardiac Stress

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Identification of MYOM2 as a candidate gene in hypertrophic cardiomyopathy and Tetralogy of Fallot, and its functional evaluation in the Drosophila heart

Disease Models & Mechanisms ◽

10.1242/dmm.045377 ◽

2020 ◽

Vol 13 (12) ◽

pp. dmm045377

Author(s):

Emilie Auxerre-Plantié ◽

Tanja Nielsen ◽

Marcel Grunert ◽

Olga Olejniczak ◽

Andreas Perrot ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Candidate Gene ◽

Tetralogy Of Fallot ◽

Heart Function ◽

Heart Diseases ◽

Critical Role ◽

Disease Genes ◽

Compound Heterozygous ◽

Functional Evaluation ◽

Myosin Binding

ABSTRACTThe causal genetic underpinnings of congenital heart diseases, which are often complex and multigenic, are still far from understood. Moreover, there are also predominantly monogenic heart defects, such as cardiomyopathies, with known disease genes for the majority of cases. In this study, we identified mutations in myomesin 2 (MYOM2) in patients with Tetralogy of Fallot (TOF), the most common cyanotic heart malformation, as well as in patients with hypertrophic cardiomyopathy (HCM), who do not exhibit any mutations in the known disease genes. MYOM2 is a major component of the myofibrillar M-band of the sarcomere, and a hub gene within interactions of sarcomere genes. We show that patient-derived cardiomyocytes exhibit myofibrillar disarray and reduced passive force with increasing sarcomere lengths. Moreover, our comprehensive functional analyses in the Drosophila animal model reveal that the so far uncharacterized fly gene CG14964 [herein referred to as Drosophila myomesin and myosin binding protein (dMnM)] may be an ortholog of MYOM2, as well as other myosin binding proteins. Its partial loss of function or moderate cardiac knockdown results in cardiac dilation, whereas more severely reduced function causes a constricted phenotype and an increase in sarcomere myosin protein. Moreover, compound heterozygous combinations of CG14964 and the sarcomere gene Mhc (MYH6/7) exhibited synergistic genetic interactions. In summary, our results suggest that MYOM2 not only plays a critical role in maintaining robust heart function but may also be a candidate gene for heart diseases such as HCM and TOF, as it is clearly involved in the development of the heart.This article has an associated First Person interview with Emilie Auxerre-Plantié and Tanja Nielsen, joint first authors of the paper.

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Cardiac stress tests – which one should I choose?

Acute Medicine Journal ◽

10.52964/amja.0256 ◽

2010 ◽

Vol 9 (1) ◽

pp. 3-7

Author(s):

Dhrubo Rakhit ◽

◽

Catherine Blakemore ◽

Keyword(s):

Chest Pain ◽

Stress Tests ◽

Stress Imaging ◽

Common Cause ◽

Medical Unit ◽

Cardiac Stress ◽

Acute Medical Unit ◽

Basic Understanding

Chest pain is a common cause of presentation to the Acute Medical Unit and the use of cardiac stress imaging in these patients is becoming more widespread. This article aims to provide Acute Physicians with a basic understanding of the different modalities and how to select a particular test for a given patient.

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Abstract 2594: Coronary Multidetector Computed Tomography in the Prognostic Assessment of Patients with Equivocal or Mildly Abnormal Non-Invasive Cardiac Stress Tests

Circulation ◽

10.1161/circ.116.suppl_16.ii_574-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Clerio Azevedo ◽

Mariane Spotti ◽

Sabrina Bezerra ◽

Marcelo Hadlich ◽

Humberto Villacorta ◽

...

Keyword(s):

Computed Tomography ◽

Coronary Artery ◽

Coronary Angiography ◽

Confidence Interval ◽

Coronary Stenosis ◽

Atherosclerotic Plaques ◽

Stress Tests ◽

Cardiac Stress ◽

Non Invasive ◽

Mdct Coronary Angiography

Background: Patients with low or moderate pre-test probability of significant coronary artery disease (CAD) and equivocal or mildly abnormal non-invasive cardiac stress tests represent a frequent management challenge. Coronary multidetector computed tomography (MDCT) has been shown to have excellent diagnostic accuracy to exclude the presence of significant CAD. Methods: The study included 218 patients (mean age 59±12 years, 60% male) with equivocal or mildly abnormal exercise electrocardiography (n=93), stress SPECT perfusion scans (n=121), stress echocardiography (n=3) and stress cardiac MRI (n=1). Patients were either asymptomatic (n=113) or had atypical chest pain (n=105). All patients underwent contrast-enhanced 64-slice MDCT coronary angiography and datasets were evaluated for the presence of coronary atherosclerotic plaques and significant coronary artery stenosis. Patients were followed for 8±3 months and the endpoints evaluated were: cardiac death, myocardial infarction, revascularization procedure performed >3 months after MDCT coronary angiography and unstable angina requiring hospitalization. Results: MDCT coronary angiography was either normal (n=90; 41%), demonstrated non-obstructive coronary atherosclerotic plaques (n=66; 30%) or exhibited significant coronary stenosis (n=62; 29%). Event-free survival was 100% for patients with normal coronary angiography, 98% for patients with non-obstructive plaques and 92% for patients with coronary stenosis (log-rank test P=0.01). One patient with a non-obstructive plaque involving the left main coronary artery died following an AMI (hazard ratio, 0.38; 95% confidence interval, 0.04 to 3.24). Among patients with coronary stenosis, 3 underwent revascularization procedures and 2 died (hazard ratio, 12.59; 95% confidence interval, 1.47 to 107.86). Conclusion: Among patients with equivocal or mildly abnormal non-invasive cardiac stress tests, a normal MDCT coronary angiography is associated with a very low risk for subsequent cardiac events. Further studies are necessary to determine the clinical significance of non-obstructive atherosclerotic plaques detected by MDCT coronary angiography in this patient population.

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