Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB
[thumbnail of Supplementary Information] Other (Supplementary Information)
4MB

Item Type:Article
Title:Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension
Creators Name: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. and Kreutz, R.
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:Cardiac Hypertrophy, Cpxm2, DOCA-salt Hypertension, Genetics, Knock-Out Mice, Animals, Mice, Rats
Source:Hypertension Research
ISSN:0916-9636
Publisher:Nature Publishing Group
Volume:45
Page Range:292-307
Date:January 2022
Official Publication:https://doi.org/10.1038/s41440-021-00826-8
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library