Key result
Recurrent exposure to subclinical lipopolysaccharide in mice induced cardiac fibrosis after 2-4 weeks, associated with early decreases in miR-29c and increases in NOX2 expression.
Recurrent exposure to subclinical LPS induces cardiac fibrosis in mice, mediated early by decreased miR-29c and increased NOX2 expression.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for subclinical inflammation in cardiac fibrosis; leaves open human relevance and should not change practice.
BACKGROUND: Exposure to subclinical levels of lipopolysaccharide (LPS) occurs commonly and is seemingly well tolerated. However, recurrent LPS exposure induces cardiac fibrosis over 2 to 3 months in a murine model, not mediated by the renin-angiotensin system. Subclinical LPS induces cardiac fibrosis by unique mechanisms. METHODS: In C57/Bl6 mice, LPS (10 mg/kg) or saline (control) were injected intraperitoneally once a week for 1-4 weeks. Mice showed no signs of distress, change in activity, appetite, or weight loss. Mice were euthanized after 3 days, 1, 2, or 4 weeks to measure cardiac expression of fibrosis-related genes and potential mediators (measured by QRT-PCR), including micro-RNA (miR) and NADPH oxidase (NOX). Collagen fraction area of the left ventricle was measured with picrosirius red staining. Cardiac fibroblasts isolated from adult mouse hearts were incubated with 0, 0.1, 1.0 or 10 ng/ml LPS for 48 hours. RESULTS: Cardiac miR expression profiling demonstrated decreased miR-29c after 3 and 7 days following LPS, which were confirmed by QRT-PCR. The earliest changes in fibrosis-related genes and mediators that occurred 3 days after LPS were increased cardiac expression of TIMP-1 and NOX-2 (but not of NOX-4). This persisted at 1 and 2 weeks, with additional increases in collagen Iα1, collagen IIIα1, MMP2, MMP9, TIMP1, TIMP2, and periostin. There was no change in TGF-β or connective tissue growth factor. Collagen fraction area of the left ventricle increased after 2 and 4 weeks of LPS. LPS decreased miR-29c and increased NOX-2 in isolated cardiac fibroblasts. CONCLUSIONS: Recurrent exposure to subclinical LPS induces cardiac fibrosis after 2-4 weeks. Early changes 3 days after LPS were decreased miR-29c and increased NOX2 and TIMP1, which persisted at 1 and 2 weeks, along with widespread activation of fibrosis-related genes. Decreased miR-29c and increased NOX2, which induce cardiac fibrosis in other conditions, may uniquely mediate LPS-induced cardiac fibrosis.
No takes yet. Share an insight, caveat, or question.
Lew et al. (2014) studied Myocardial Fibrosis. Lipopolysaccharide (LPS) vs. Saline was evaluated on Cardiac expression of miR-29c and NOX2, and collagen fraction area (p=<0.05). Recurrent exposure to subclinical lipopolysaccharide in mice induced cardiac fibrosis after 2-4 weeks, associated with early decreases in miR-29c and increases in NOX2 expression.
Synapse has enriched 10 related papers. Consider them for comparative context: