Priming with synthetic oligonucleotides attenuates pressure overload-induced inflammation and cardiac hypertrophy in mice
Velten M, Duerr GD, Pessies T, Schild J, Lohner R, Mersmann J, Zacharowski K, Klaschik S, Hilbert T, Hoeft A, Baumgarten G, Meyer R, Boehm O, Knuefermann P, Dewald O (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 96
Pages Range: 422-432
Journal Issue: 3
DOI: 10.1093/cvr/cvs280
Abstract
AimsInflammation and Toll-like receptor (TLR) signalling have been linked to the development of cardiac hypertrophy following transverse aortic constriction (TAC). In the present study, we investigated whether pre-treatment with the synthetic TLR9 ligands 1668-thioate or 1612-thioate modulates the progression of TAC-induced cardiac inflammation and hypertrophy.Methods and resultsC57BL/6N-mice were pre-treated with 1668-thioate, 1612-thioate (0.25 nmol/g, i.p.), or phosphate-buffered saline 16 h prior to TAC or sham surgery. Heart-weight/body-weight ratio (HW/BW), cardiomyocyte cell size, cellular macrophage accumulation, myofibroblast differentiation, and collagen deposition were investigated for up to 28 days. Cardiac function was monitored using a pressure-volume catheter and M-mode echocardiography. Inflammatory gene expression in the heart was analysed via gene array, while the time course of mRNA expression of key inflammatory mediators was assessed via RT-qPCR. TAC increased the HW/BW ratio and cardiomyocyte cell size and induced macrophage accumulation, myofibroblast differentiation, and collagen deposition. These changes were accompanied by cardiac inflammation and a significant loss of left ventricular function. Pre-treatment with cytosine-phosphate-guanine (CpG)-containing 1668-thioate attenuated the inflammatory response, the progression of cardiac hypertrophy, and cardiac remodelling, which resulted in a prolonged preservation of left ventricular function. These changes were induced to a smaller extent by the use of the non-CG-containing oligodeoxynucleotide 1612-thioate.ConclusionPre-treatment with 1668-thioate attenuated cardiac hypertrophy following pressure overload, possibly by modifying the hypertrophy-induced inflammatory response, thereby reducing cardiac growth and fibrosis as well as delaying loss of cardiac function. © 2012 The Author.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Bonn
Germany (DE)
Universitätsklinikum Frankfurt am Main (KGU)
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Germany (DE)
Universitätsklinikum Frankfurt am Main (KGU)
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
How to cite
APA:
Velten, M., Duerr, G.D., Pessies, T., Schild, J., Lohner, R., Mersmann, J.,... Dewald, O. (2012). Priming with synthetic oligonucleotides attenuates pressure overload-induced inflammation and cardiac hypertrophy in mice. Cardiovascular Research, 96(3), 422-432. https://doi.org/10.1093/cvr/cvs280
MLA:
Velten, Markus, et al. "Priming with synthetic oligonucleotides attenuates pressure overload-induced inflammation and cardiac hypertrophy in mice." Cardiovascular Research 96.3 (2012): 422-432.
BibTeX: Download