Kinetic mRNA Profiling in a Rat Model of Left-Ventricular Hypertrophy Reveals Early Expression of Chemokines and Their ReceptorsReport as inadecuate

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Left-ventricular hypertrophy LVH, a risk factor for heart failure and death, is characterized by cardiomyocyte hypertrophy, interstitial cell proliferation, and leukocyte infiltration. Chemokines interacting with G protein-coupled chemokine receptors may play a role in LVH development by promoting recruitment of activated leukocytes or modulating left-ventricular remodeling. Using a pressure overload-induced kinetic model of LVH in rats, we examined during 14 days the expression over time of chemokine and chemokine receptor mRNAs in left ventricles from aortic-banded vs sham-operated animals. Two phases were clearly distinguished: an inflammatory phase D3-D5 with overexpression of inflammatory genes such as il-1ß, tnfa, nlrp3, and the rela subunit of nf-kb, and a hypertrophic phase D7-D14 where anp overexpression was accompanied by a heart weight-body weight ratio that increased by more than 20% at D14. No cardiac dysfunction was detectable by echocardiography at the latter time point. Of the 36 chemokines and 20 chemokine receptors analyzed by a Taqman Low Density Array panel, we identified at D3 the early inflammatory phase overexpression of mRNAs for the monocyte chemotactic proteins CCL2 12-fold increase, CCL7 7-fold increase, and CCL12 3-fold increase, for the macrophage inflammatory proteins CCL3 4-fold increase, CCL4 2-fold increase, and CCL9 2-fold increase, for their receptors CCR2 4-fold increase, CCR1 3-fold increase, and CCR5 3-fold increase, and for CXCL1 8-fold increase and CXCL16 2-fold increase. During the hypertrophic phase mRNA expression of chemokines and receptors returned to the baseline levels observed at D0. Hence, this first exhaustive study of chemokine and chemokine receptor mRNA expression kinetics reports early expression of monocyte-macrophage-related chemokines and their receptors during the development of LVH in rats, followed by regulation of inflammation as LVH progresses.

Author: Simona Nemska, Laurent Monassier, Max Gassmann, Nelly Frossard , Reza Tavakoli



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