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Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities

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Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities. / Judge, Daniel P; Neamatalla, Hany; Norris, Russel A; Levine, Robert L; Butcher, Jonathan T; Vignier, Nicolas; Kang, Kevin H; Nguyen, Quangtung; Bruneval, Patrick; Perier, Marie-Cécile; Messas, Emmanuel; Jeunemaitre, Xavier; de Vlaming, Annemarieke; Markwald, Roger; Carrier, Lucie; Hagège, Albert A.

In: J CARDIOVASC DEV DIS, Vol. 2, No. 2, 2015, p. 48-65.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Judge, DP, Neamatalla, H, Norris, RA, Levine, RL, Butcher, JT, Vignier, N, Kang, KH, Nguyen, Q, Bruneval, P, Perier, M-C, Messas, E, Jeunemaitre, X, de Vlaming, A, Markwald, R, Carrier, L & Hagège, AA 2015, 'Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities', J CARDIOVASC DEV DIS, vol. 2, no. 2, pp. 48-65.

APA

Judge, D. P., Neamatalla, H., Norris, R. A., Levine, R. L., Butcher, J. T., Vignier, N., Kang, K. H., Nguyen, Q., Bruneval, P., Perier, M-C., Messas, E., Jeunemaitre, X., de Vlaming, A., Markwald, R., Carrier, L., & Hagège, A. A. (2015). Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities. J CARDIOVASC DEV DIS, 2(2), 48-65.

Vancouver

Judge DP, Neamatalla H, Norris RA, Levine RL, Butcher JT, Vignier N et al. Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities. J CARDIOVASC DEV DIS. 2015;2(2):48-65.

Bibtex

@article{e1a621f5adae4552bc131ee8cff150be,
title = "Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities",
abstract = "MYBPC3 mutations cause hypertrophic cardiomyopathy, which is frequently associated with mitral valve (MV) pathology. We reasoned that increased MV size is caused by localized growth factors with paracrine effects. We used high-resolution echocardiography to compare Mybpc3-null, heterozygous, and wild-type mice (n = 84, aged 3–6 months) and micro-CT for MV volume (n = 6, age 6 months). Mybpc3-null mice showed left ventricular hypertrophy, dilation, and systolic dysfunction compared to heterozygous and wild-type mice, but no systolic anterior motion of the MV or left ventricular outflow obstruction. Compared to wild-type mice, echocardiographic anterior leaflet length (adjusted for left ventricular size) was greatest in Mybpc3-null mice (1.92 ± 0.08 vs. 1.72 ± 0.08 mm, p < 0.001), as was combined leaflet thickness (0.23 ± 0.04 vs. 0.15 ± 0.02 mm, p < 0.001). Micro-CT analyses of Mybpc3-null mice demonstrated increased MV volume (0.47 ± 0.06 vs. 0.15 ± 0.06 mm3, p = 0.018) and thickness (0.35 ± 0.04 vs. 0.12 ± 0.04 mm, p = 0.002), coincident with increased markers of TGFβ activity compared to heterozygous and wild-type littermates. Similarly, excised MV from a patient with MYBPC3 mutation showed increased TGFβ activity. We conclude that MYBPC3 deficiency causes hypertrophic cardiomyopathy with increased MV leaflet length and thickness despite the absence of left ventricular outflow-tract obstruction, in parallel with increased TGFβ activity. MV changes in hypertrophic cardiomyopathy may be due to paracrine effects, which represent targets for therapeutic studies. ",
author = "Judge, {Daniel P} and Hany Neamatalla and Norris, {Russel A} and Levine, {Robert L} and Butcher, {Jonathan T} and Nicolas Vignier and Kang, {Kevin H} and Quangtung Nguyen and Patrick Bruneval and Marie-C{\'e}cile Perier and Emmanuel Messas and Xavier Jeunemaitre and {de Vlaming}, Annemarieke and Roger Markwald and Lucie Carrier and Hag{\`e}ge, {Albert A}",
year = "2015",
language = "English",
volume = "2",
pages = "48--65",
journal = "J CARDIOVASC DEV DIS",
issn = "2308-3425",
publisher = "MDPI AG",
number = "2",

}

RIS

TY - JOUR

T1 - Targeted Mybpc3 knock-out mice with cardiac hypertrophy exhibit structural mitral valve abnormalities

AU - Judge, Daniel P

AU - Neamatalla, Hany

AU - Norris, Russel A

AU - Levine, Robert L

AU - Butcher, Jonathan T

AU - Vignier, Nicolas

AU - Kang, Kevin H

AU - Nguyen, Quangtung

AU - Bruneval, Patrick

AU - Perier, Marie-Cécile

AU - Messas, Emmanuel

AU - Jeunemaitre, Xavier

AU - de Vlaming, Annemarieke

AU - Markwald, Roger

AU - Carrier, Lucie

AU - Hagège, Albert A

PY - 2015

Y1 - 2015

N2 - MYBPC3 mutations cause hypertrophic cardiomyopathy, which is frequently associated with mitral valve (MV) pathology. We reasoned that increased MV size is caused by localized growth factors with paracrine effects. We used high-resolution echocardiography to compare Mybpc3-null, heterozygous, and wild-type mice (n = 84, aged 3–6 months) and micro-CT for MV volume (n = 6, age 6 months). Mybpc3-null mice showed left ventricular hypertrophy, dilation, and systolic dysfunction compared to heterozygous and wild-type mice, but no systolic anterior motion of the MV or left ventricular outflow obstruction. Compared to wild-type mice, echocardiographic anterior leaflet length (adjusted for left ventricular size) was greatest in Mybpc3-null mice (1.92 ± 0.08 vs. 1.72 ± 0.08 mm, p < 0.001), as was combined leaflet thickness (0.23 ± 0.04 vs. 0.15 ± 0.02 mm, p < 0.001). Micro-CT analyses of Mybpc3-null mice demonstrated increased MV volume (0.47 ± 0.06 vs. 0.15 ± 0.06 mm3, p = 0.018) and thickness (0.35 ± 0.04 vs. 0.12 ± 0.04 mm, p = 0.002), coincident with increased markers of TGFβ activity compared to heterozygous and wild-type littermates. Similarly, excised MV from a patient with MYBPC3 mutation showed increased TGFβ activity. We conclude that MYBPC3 deficiency causes hypertrophic cardiomyopathy with increased MV leaflet length and thickness despite the absence of left ventricular outflow-tract obstruction, in parallel with increased TGFβ activity. MV changes in hypertrophic cardiomyopathy may be due to paracrine effects, which represent targets for therapeutic studies.

AB - MYBPC3 mutations cause hypertrophic cardiomyopathy, which is frequently associated with mitral valve (MV) pathology. We reasoned that increased MV size is caused by localized growth factors with paracrine effects. We used high-resolution echocardiography to compare Mybpc3-null, heterozygous, and wild-type mice (n = 84, aged 3–6 months) and micro-CT for MV volume (n = 6, age 6 months). Mybpc3-null mice showed left ventricular hypertrophy, dilation, and systolic dysfunction compared to heterozygous and wild-type mice, but no systolic anterior motion of the MV or left ventricular outflow obstruction. Compared to wild-type mice, echocardiographic anterior leaflet length (adjusted for left ventricular size) was greatest in Mybpc3-null mice (1.92 ± 0.08 vs. 1.72 ± 0.08 mm, p < 0.001), as was combined leaflet thickness (0.23 ± 0.04 vs. 0.15 ± 0.02 mm, p < 0.001). Micro-CT analyses of Mybpc3-null mice demonstrated increased MV volume (0.47 ± 0.06 vs. 0.15 ± 0.06 mm3, p = 0.018) and thickness (0.35 ± 0.04 vs. 0.12 ± 0.04 mm, p = 0.002), coincident with increased markers of TGFβ activity compared to heterozygous and wild-type littermates. Similarly, excised MV from a patient with MYBPC3 mutation showed increased TGFβ activity. We conclude that MYBPC3 deficiency causes hypertrophic cardiomyopathy with increased MV leaflet length and thickness despite the absence of left ventricular outflow-tract obstruction, in parallel with increased TGFβ activity. MV changes in hypertrophic cardiomyopathy may be due to paracrine effects, which represent targets for therapeutic studies.

M3 - SCORING: Journal article

VL - 2

SP - 48

EP - 65

JO - J CARDIOVASC DEV DIS

JF - J CARDIOVASC DEV DIS

SN - 2308-3425

IS - 2

ER -