Selective translation of mRNAs in the left ventricular myocardium of the mouse in response to acute pressure overload
- PMID: 18036610
- PMCID: PMC2246077
- DOI: 10.1016/j.yjmcc.2007.10.011
Selective translation of mRNAs in the left ventricular myocardium of the mouse in response to acute pressure overload
Abstract
During pressure overload hypertrophy, selective changes in cardiac gene expression occur that regulate growth and modify the structural and functional properties of the myocardium. To determine the role of translational mechanisms, a murine model of transverse aortic constriction was used to screen a set of specified mRNAs for changes in translational activity by measuring incorporation into polysomes in response to acute pressure overload. Candidate mRNAs were selected on the basis of two main criteria: (1) the 5'-untranslated region of the mRNA contains an excessive amount of secondary structure (DeltaG<-50 kCal/mol), which is postulated to regulate efficiency of translation, and (2) the protein product has been implicated in the regulation of cardiac hypertrophy. After 24 h of transverse aortic constriction, homogenates derived from the left ventricle were layered onto 15-50% linear sucrose gradients and resolved into monosome fractions (messenger ribonucleoprotein particles) and polysome fractions by density gradient ultracentrifugation. The levels of mRNA in each fraction were quantified by real-time RT-PCR. The screen revealed that pressure overload increased translational activity of 6 candidate mRNAs as determined by a significant increase in the percentage of total mRNA incorporated into the polysome fractions. The mRNAs code for several functional classes of proteins linked to cardiac hypertrophy: the transcription factors c-myc, c-jun and MEF2D, growth factors VEGF and FGF-2 and the E3 ubiquitin ligase MDM2. These studies demonstrate that acute pressure overload alters cardiac gene expression by mechanisms that selectively regulate translational activity of specific mRNAs.
Figures




Similar articles
-
CCN2/CTGF attenuates myocardial hypertrophy and cardiac dysfunction upon chronic pressure-overload.Int J Cardiol. 2013 Oct 3;168(3):2049-56. doi: 10.1016/j.ijcard.2013.01.165. Epub 2013 Feb 26. Int J Cardiol. 2013. PMID: 23452880
-
Differential cardiac hypertrophy and signaling pathways in pressure versus volume overload.Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H552-H562. doi: 10.1152/ajpheart.00212.2017. Epub 2017 Dec 1. Am J Physiol Heart Circ Physiol. 2018. PMID: 29196344
-
Cathepsin K knockout alleviates pressure overload-induced cardiac hypertrophy.Hypertension. 2013 Jun;61(6):1184-92. doi: 10.1161/HYPERTENSIONAHA.111.00947. Epub 2013 Mar 25. Hypertension. 2013. PMID: 23529168 Free PMC article.
-
Toll-like receptor-2 mediates adaptive cardiac hypertrophy in response to pressure overload through interleukin-1β upregulation via nuclear factor κB activation.J Am Heart Assoc. 2013 Nov 18;2(6):e000267. doi: 10.1161/JAHA.113.000267. J Am Heart Assoc. 2013. PMID: 24249711 Free PMC article.
-
T₁ mapping detects pharmacological retardation of diffuse cardiac fibrosis in mouse pressure-overload hypertrophy.Circ Cardiovasc Imaging. 2014 Mar;7(2):240-9. doi: 10.1161/CIRCIMAGING.113.000993. Epub 2014 Jan 14. Circ Cardiovasc Imaging. 2014. PMID: 24425501
Cited by
-
The ins and outs of calcium in heart failure.Circ Res. 2008 Jun 6;102(11):1301-3. doi: 10.1161/CIRCRESAHA.108.178095. Circ Res. 2008. PMID: 18535266 Free PMC article. No abstract available.
-
Translating Translation to Mechanisms of Cardiac Hypertrophy.J Cardiovasc Dev Dis. 2020 Mar 10;7(1):9. doi: 10.3390/jcdd7010009. J Cardiovasc Dev Dis. 2020. PMID: 32164190 Free PMC article. Review.
-
Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila.Development. 2009 Mar;136(6):983-93. doi: 10.1242/dev.027466. Epub 2009 Feb 11. Development. 2009. PMID: 19211682 Free PMC article.
-
Regulation of Protein Synthesis at the Translational Level: Novel Findings in Cardiovascular Biology.Biomolecules. 2025 May 9;15(5):692. doi: 10.3390/biom15050692. Biomolecules. 2025. PMID: 40427584 Free PMC article. Review.
-
Bone marrow SSEA1+ cells support the myocardium in cardiac pressure overload.PLoS One. 2013 Jul 9;8(7):e68528. doi: 10.1371/journal.pone.0068528. Print 2013. PLoS One. 2013. PMID: 23874657 Free PMC article.
References
-
- Berenji K, Drazner MH, Rothermel BA, Hill JA. Does load-induced ventricular hypertrophy progress to systolic heart failure? Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H8–H16. - PubMed
-
- Cooper G., IV Cardiocyte adaptation to chronically altered load. Annu Rev Physiol. 1987;49:501–18. - PubMed
-
- Marino TA, Kent RL, Uboh CE, Fernandez E, Thompson EW, Cooper G., IV Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle. Am J Physiol. 1985 Aug;249(2 Pt 2):H371–9. - PubMed
-
- Swynghedauw B. Phenotypic plasticity of adult myocardium: molecular mechanisms. J Exp Biol. 2006 Jun;209(Pt 12):2320–7. - PubMed
-
- Hannan RD, Jenkins A, Jenkins AK, Brandenburger Y. Cardiac hypertrophy: a matter of translation. Clin Exp Pharmacol Physiol. 2003 Aug;30(8):517–27. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous