Aortic banding in rats induced an early inflammatory phase at days 3-5 with significant overexpression of chemokines, including a 12-fold increase in CCL2, which returned to baseline as left-ventricular hypertrophy progressed by day 14.
In a rat model of pressure overload-induced LVH, an early inflammatory phase characterized by chemokine and receptor overexpression precedes the development of compensated cardiac hypertrophy.
Estimación del efecto: 12.2-fold increase
Tasa de eventos absoluta: 12.2% vs 1%
valor p: p=<0.01
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.
Nemska et al. (Mon,) conducted a other in Left-ventricular hypertrophy (n=86). Aortic banding vs. Sham operation was evaluated on CCL2 mRNA expression at Day 3 (12.2-fold increase, p=<0.01). Aortic banding in rats induced an early inflammatory phase at days 3-5 with significant overexpression of chemokines, including a 12-fold increase in CCL2, which returned to baseline as left-ventricular hypertrophy progressed by day 14.