You are not logged in.

Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22

Prestes, Priscilla R., Marques, Francine Z., Lopez-Campos, Guillermo, Booth, Scott A., McGlynn, Maree, Lewandowski, Paul, Delbridge, Lea M.D., Harrap, Stephen B. and Charchar, Fadi J. 2016, Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22, Journal of hypertension, vol. 34, no. 5, pp. 950-958, doi: 10.1097/HJH.0000000000000875.

Attached Files
Name Description MIMEType Size Downloads

Title Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22
Author(s) Prestes, Priscilla R.
Marques, Francine Z.
Lopez-Campos, Guillermo
Booth, Scott A.
McGlynn, Maree
Lewandowski, Paul
Delbridge, Lea M.D.
Harrap, Stephen B.
Charchar, Fadi J.
Journal name Journal of hypertension
Volume number 34
Issue number 5
Start page 950
End page 958
Total pages 9
Publisher Wolters Kluwer
Place of publication Philadelphia, Pa.
Publication date 2016-05
ISSN 0263-6352
1473-5598
Keyword(s) animal models
cardiomyopathy
functional genomics
microarray
transcriptome
Science & Technology
Life Sciences & Biomedicine
Peripheral Vascular Disease
Cardiovascular System & Cardiology
LEFT-VENTRICULAR MASS
LARGE GENE LISTS
RING FINGER 1
HEART SIZE
IN-VIVO
GENOME
DISEASE
HERITABILITY
GENERATION
TRANSFORM
Summary BACKGROUND: Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR).

METHODS AND RESULTS: To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHR × NHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P < 0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r = -0.16, P = 0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F = 10.35, P < 0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy.

CONCLUSION: Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.
Language eng
DOI 10.1097/HJH.0000000000000875
Field of Research 1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Socio Economic Objective 920103 Cardiovascular System and Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Wolters Kluwer Health
Persistent URL http://hdl.handle.net/10536/DRO/DU:30085770

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 31 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Tue, 30 Aug 2016, 14:42:45 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.