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Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension

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Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension. / Grabowski, Katja; Herlan, Laura; Witten, Anika; Qadri, Fatimunnisa; Eisenreich, Andreas; Lindner, Diana; Schädlich, Martin; Schulz, Angela; Subrova, Jana; Mhatre, Ketaki Nitin; Primessnig, Uwe; Plehm, Ralph; van Linthout, Sophie; Escher, Felicitas; Bader, Michael; Stoll, Monika; Westermann, Dirk; Heinzel, Frank R; Kreutz, Reinhold.

In: HYPERTENS RES, Vol. 45, No. 2, 02.2022, p. 292-307.

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

Harvard

Grabowski, K, Herlan, L, Witten, A, Qadri, F, Eisenreich, A, Lindner, D, Schädlich, M, Schulz, A, Subrova, J, Mhatre, KN, Primessnig, U, Plehm, R, van Linthout, S, Escher, F, Bader, M, Stoll, M, Westermann, D, Heinzel, FR & Kreutz, R 2022, 'Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension', HYPERTENS RES, vol. 45, no. 2, pp. 292-307. https://doi.org/10.1038/s41440-021-00826-8

APA

Grabowski, K., Herlan, L., Witten, A., Qadri, F., Eisenreich, A., Lindner, D., Schädlich, M., Schulz, A., Subrova, J., Mhatre, K. N., Primessnig, U., Plehm, R., van Linthout, S., Escher, F., Bader, M., Stoll, M., Westermann, D., Heinzel, F. R., & Kreutz, R. (2022). Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension. HYPERTENS RES, 45(2), 292-307. https://doi.org/10.1038/s41440-021-00826-8

Vancouver

Grabowski K, Herlan L, Witten A, Qadri F, Eisenreich A, Lindner D et al. Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension. HYPERTENS RES. 2022 Feb;45(2):292-307. https://doi.org/10.1038/s41440-021-00826-8

Bibtex

@article{3fb25259dea24e8b8b5a35a02d1f3ab3,
title = "Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension",
abstract = "Treatment of hypertension-mediated cardiac damage with left ventricular (LV) hypertrophy (LVH) and heart failure remains challenging. To identify novel targets, we performed comparative transcriptome analysis between genetic models derived from stroke-prone spontaneously hypertensive rats (SHRSP). Here, we identified carboxypeptidase X 2 (Cpxm2) as a genetic locus affecting LV mass. Analysis of isolated rat cardiomyocytes and cardiofibroblasts indicated Cpxm2 expression and intrinsic upregulation in genetic hypertension. Immunostaining indicated that CPXM2 associates with the t-tubule network of cardiomyocytes. The functional role of Cpxm2 was further investigated in Cpxm2-deficient (KO) and wild-type (WT) mice exposed to deoxycorticosterone acetate (DOCA). WT and KO animals developed severe and similar systolic hypertension in response to DOCA. WT mice developed severe LV damage, including increases in LV masses and diameters, impairment of LV systolic and diastolic function and reduced ejection fraction. These changes were significantly ameliorated or even normalized (i.e., ejection fraction) in KO-DOCA animals. LV transcriptome analysis showed a molecular cardiac hypertrophy/remodeling signature in WT but not KO mice with significant upregulation of 1234 transcripts, including Cpxm2, in response to DOCA. Analysis of endomyocardial biopsies from patients with cardiac hypertrophy indicated significant upregulation of CPXM2 expression. These data support further translational investigation of CPXM2.",
keywords = "Animals, Carboxypeptidases, Cardiomegaly/genetics, Humans, Hypertension, Hypertrophy, Left Ventricular, Mice, Myocytes, Cardiac, Rats",
author = "Katja Grabowski and Laura Herlan and Anika Witten and Fatimunnisa Qadri and Andreas Eisenreich and Diana Lindner and Martin Sch{\"a}dlich and Angela Schulz and Jana Subrova and Mhatre, {Ketaki Nitin} and Uwe Primessnig and Ralph Plehm and {van Linthout}, Sophie and Felicitas Escher and Michael Bader and Monika Stoll and Dirk Westermann and Heinzel, {Frank R} and Reinhold Kreutz",
note = "{\textcopyright} 2021. The Author(s).",
year = "2022",
month = feb,
doi = "10.1038/s41440-021-00826-8",
language = "English",
volume = "45",
pages = "292--307",
journal = "HYPERTENS RES",
issn = "0916-9636",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension

AU - Grabowski, Katja

AU - Herlan, Laura

AU - Witten, Anika

AU - Qadri, Fatimunnisa

AU - Eisenreich, Andreas

AU - Lindner, Diana

AU - Schädlich, Martin

AU - Schulz, Angela

AU - Subrova, Jana

AU - Mhatre, Ketaki Nitin

AU - Primessnig, Uwe

AU - Plehm, Ralph

AU - van Linthout, Sophie

AU - Escher, Felicitas

AU - Bader, Michael

AU - Stoll, Monika

AU - Westermann, Dirk

AU - Heinzel, Frank R

AU - Kreutz, Reinhold

N1 - © 2021. The Author(s).

PY - 2022/2

Y1 - 2022/2

N2 - Treatment of hypertension-mediated cardiac damage with left ventricular (LV) hypertrophy (LVH) and heart failure remains challenging. To identify novel targets, we performed comparative transcriptome analysis between genetic models derived from stroke-prone spontaneously hypertensive rats (SHRSP). Here, we identified carboxypeptidase X 2 (Cpxm2) as a genetic locus affecting LV mass. Analysis of isolated rat cardiomyocytes and cardiofibroblasts indicated Cpxm2 expression and intrinsic upregulation in genetic hypertension. Immunostaining indicated that CPXM2 associates with the t-tubule network of cardiomyocytes. The functional role of Cpxm2 was further investigated in Cpxm2-deficient (KO) and wild-type (WT) mice exposed to deoxycorticosterone acetate (DOCA). WT and KO animals developed severe and similar systolic hypertension in response to DOCA. WT mice developed severe LV damage, including increases in LV masses and diameters, impairment of LV systolic and diastolic function and reduced ejection fraction. These changes were significantly ameliorated or even normalized (i.e., ejection fraction) in KO-DOCA animals. LV transcriptome analysis showed a molecular cardiac hypertrophy/remodeling signature in WT but not KO mice with significant upregulation of 1234 transcripts, including Cpxm2, in response to DOCA. Analysis of endomyocardial biopsies from patients with cardiac hypertrophy indicated significant upregulation of CPXM2 expression. These data support further translational investigation of CPXM2.

AB - Treatment of hypertension-mediated cardiac damage with left ventricular (LV) hypertrophy (LVH) and heart failure remains challenging. To identify novel targets, we performed comparative transcriptome analysis between genetic models derived from stroke-prone spontaneously hypertensive rats (SHRSP). Here, we identified carboxypeptidase X 2 (Cpxm2) as a genetic locus affecting LV mass. Analysis of isolated rat cardiomyocytes and cardiofibroblasts indicated Cpxm2 expression and intrinsic upregulation in genetic hypertension. Immunostaining indicated that CPXM2 associates with the t-tubule network of cardiomyocytes. The functional role of Cpxm2 was further investigated in Cpxm2-deficient (KO) and wild-type (WT) mice exposed to deoxycorticosterone acetate (DOCA). WT and KO animals developed severe and similar systolic hypertension in response to DOCA. WT mice developed severe LV damage, including increases in LV masses and diameters, impairment of LV systolic and diastolic function and reduced ejection fraction. These changes were significantly ameliorated or even normalized (i.e., ejection fraction) in KO-DOCA animals. LV transcriptome analysis showed a molecular cardiac hypertrophy/remodeling signature in WT but not KO mice with significant upregulation of 1234 transcripts, including Cpxm2, in response to DOCA. Analysis of endomyocardial biopsies from patients with cardiac hypertrophy indicated significant upregulation of CPXM2 expression. These data support further translational investigation of CPXM2.

KW - Animals

KW - Carboxypeptidases

KW - Cardiomegaly/genetics

KW - Humans

KW - Hypertension

KW - Hypertrophy, Left Ventricular

KW - Mice

KW - Myocytes, Cardiac

KW - Rats

U2 - 10.1038/s41440-021-00826-8

DO - 10.1038/s41440-021-00826-8

M3 - SCORING: Journal article

C2 - 34916661

VL - 45

SP - 292

EP - 307

JO - HYPERTENS RES

JF - HYPERTENS RES

SN - 0916-9636

IS - 2

ER -