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FHL2 expression and variants in hypertrophic cardiomyopathy

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FHL2 expression and variants in hypertrophic cardiomyopathy. / Friedrich, Felix W; Reischmann, Silke; Schwalm, Aileen; Unger, Andreas; Ramanujam, Deepak; Münch, Julia; Müller, Oliver J; Hengstenberg, Christian; Galve, Enrique; Charron, Philippe; Linke, Wolfgang A; Engelhardt, Stefan; Patten-Hamel, Monica; Richard, Pascale; van der Velden, Jolanda; Eschenhagen, Thomas; Isnard, Richard; Carrier, Lucie.

In: BASIC RES CARDIOL, Vol. 109, No. 6, 01.11.2014, p. 451.

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

Harvard

Friedrich, FW, Reischmann, S, Schwalm, A, Unger, A, Ramanujam, D, Münch, J, Müller, OJ, Hengstenberg, C, Galve, E, Charron, P, Linke, WA, Engelhardt, S, Patten-Hamel, M, Richard, P, van der Velden, J, Eschenhagen, T, Isnard, R & Carrier, L 2014, 'FHL2 expression and variants in hypertrophic cardiomyopathy', BASIC RES CARDIOL, vol. 109, no. 6, pp. 451. https://doi.org/10.1007/s00395-014-0451-8

APA

Friedrich, F. W., Reischmann, S., Schwalm, A., Unger, A., Ramanujam, D., Münch, J., Müller, O. J., Hengstenberg, C., Galve, E., Charron, P., Linke, W. A., Engelhardt, S., Patten-Hamel, M., Richard, P., van der Velden, J., Eschenhagen, T., Isnard, R., & Carrier, L. (2014). FHL2 expression and variants in hypertrophic cardiomyopathy. BASIC RES CARDIOL, 109(6), 451. https://doi.org/10.1007/s00395-014-0451-8

Vancouver

Friedrich FW, Reischmann S, Schwalm A, Unger A, Ramanujam D, Münch J et al. FHL2 expression and variants in hypertrophic cardiomyopathy. BASIC RES CARDIOL. 2014 Nov 1;109(6):451. https://doi.org/10.1007/s00395-014-0451-8

Bibtex

@article{6c396804fc6b4d11a8b2a58376374332,
title = "FHL2 expression and variants in hypertrophic cardiomyopathy",
abstract = "Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether FHL2 altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is a myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis and is mainly caused by mutations in genes coding for sarcomeric proteins. FHL2 mRNA level, FHL2 protein level and I-band-binding density were lower in HCM patients than control individuals. Screening of 121 HCM patients without mutations in established disease genes identified 2 novel (T171M, V187L) and 4 known (R177Q, N226N, D268D, P273P) FHL2 variants in unrelated HCM families. We assessed the structural and functional consequences of the nonsynonymous substitutions after adeno-associated viral-mediated gene transfer in cardiac myocytes and in 3D-engineered heart tissue (EHT). Overexpression of FHL2 wild type or nonsynonymous substitutions in cardiac myocytes markedly down-regulated α-skeletal actin and partially blunted hypertrophy induced by phenylephrine or endothelin-1. After gene transfer in EHTs, force and velocity of both contraction and relaxation were higher with T171M and V187L FHL2 variants than wild type under basal conditions. Finally, chronic phenylephrine stimulation depressed EHT function in all groups, but to a lower extent in T171M-transduced EHTs. These data suggest that (1) FHL2 is down-regulated in HCM, (2) both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes, and (3) FHL2 T171M and V187L nonsynonymous variants induced altered EHT contractility. These findings provide evidence that the 2 novel FHL2 variants could increase cardiac function in HCM.",
author = "Friedrich, {Felix W} and Silke Reischmann and Aileen Schwalm and Andreas Unger and Deepak Ramanujam and Julia M{\"u}nch and M{\"u}ller, {Oliver J} and Christian Hengstenberg and Enrique Galve and Philippe Charron and Linke, {Wolfgang A} and Stefan Engelhardt and Monica Patten-Hamel and Pascale Richard and {van der Velden}, Jolanda and Thomas Eschenhagen and Richard Isnard and Lucie Carrier",
year = "2014",
month = nov,
day = "1",
doi = "10.1007/s00395-014-0451-8",
language = "English",
volume = "109",
pages = "451",
journal = "BASIC RES CARDIOL",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "6",

}

RIS

TY - JOUR

T1 - FHL2 expression and variants in hypertrophic cardiomyopathy

AU - Friedrich, Felix W

AU - Reischmann, Silke

AU - Schwalm, Aileen

AU - Unger, Andreas

AU - Ramanujam, Deepak

AU - Münch, Julia

AU - Müller, Oliver J

AU - Hengstenberg, Christian

AU - Galve, Enrique

AU - Charron, Philippe

AU - Linke, Wolfgang A

AU - Engelhardt, Stefan

AU - Patten-Hamel, Monica

AU - Richard, Pascale

AU - van der Velden, Jolanda

AU - Eschenhagen, Thomas

AU - Isnard, Richard

AU - Carrier, Lucie

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether FHL2 altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is a myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis and is mainly caused by mutations in genes coding for sarcomeric proteins. FHL2 mRNA level, FHL2 protein level and I-band-binding density were lower in HCM patients than control individuals. Screening of 121 HCM patients without mutations in established disease genes identified 2 novel (T171M, V187L) and 4 known (R177Q, N226N, D268D, P273P) FHL2 variants in unrelated HCM families. We assessed the structural and functional consequences of the nonsynonymous substitutions after adeno-associated viral-mediated gene transfer in cardiac myocytes and in 3D-engineered heart tissue (EHT). Overexpression of FHL2 wild type or nonsynonymous substitutions in cardiac myocytes markedly down-regulated α-skeletal actin and partially blunted hypertrophy induced by phenylephrine or endothelin-1. After gene transfer in EHTs, force and velocity of both contraction and relaxation were higher with T171M and V187L FHL2 variants than wild type under basal conditions. Finally, chronic phenylephrine stimulation depressed EHT function in all groups, but to a lower extent in T171M-transduced EHTs. These data suggest that (1) FHL2 is down-regulated in HCM, (2) both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes, and (3) FHL2 T171M and V187L nonsynonymous variants induced altered EHT contractility. These findings provide evidence that the 2 novel FHL2 variants could increase cardiac function in HCM.

AB - Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether FHL2 altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is a myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis and is mainly caused by mutations in genes coding for sarcomeric proteins. FHL2 mRNA level, FHL2 protein level and I-band-binding density were lower in HCM patients than control individuals. Screening of 121 HCM patients without mutations in established disease genes identified 2 novel (T171M, V187L) and 4 known (R177Q, N226N, D268D, P273P) FHL2 variants in unrelated HCM families. We assessed the structural and functional consequences of the nonsynonymous substitutions after adeno-associated viral-mediated gene transfer in cardiac myocytes and in 3D-engineered heart tissue (EHT). Overexpression of FHL2 wild type or nonsynonymous substitutions in cardiac myocytes markedly down-regulated α-skeletal actin and partially blunted hypertrophy induced by phenylephrine or endothelin-1. After gene transfer in EHTs, force and velocity of both contraction and relaxation were higher with T171M and V187L FHL2 variants than wild type under basal conditions. Finally, chronic phenylephrine stimulation depressed EHT function in all groups, but to a lower extent in T171M-transduced EHTs. These data suggest that (1) FHL2 is down-regulated in HCM, (2) both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes, and (3) FHL2 T171M and V187L nonsynonymous variants induced altered EHT contractility. These findings provide evidence that the 2 novel FHL2 variants could increase cardiac function in HCM.

U2 - 10.1007/s00395-014-0451-8

DO - 10.1007/s00395-014-0451-8

M3 - SCORING: Journal article

C2 - 25358972

VL - 109

SP - 451

JO - BASIC RES CARDIOL

JF - BASIC RES CARDIOL

SN - 0300-8428

IS - 6

ER -