The myofibroblast plays a central role in mediating signaling pathways that cause an imbalance between collagen synthesis and degradation resulting in cardiac fibrosis. The profile of increased cardiac expression of collagen Ia1, collagen III a1, MMP2, MMP9, TIMP1, TIMP2, and periostin 2 weeks after LPS, was similar in magnitude to the changes observed after 2�C3 months of weekly exposure to subclinical LPS. Cardiac fibrosis is mediated by TGF-b and/or CTGF in several pathological conditions. LPS did not change in mRNA expression of TGF-b or CTGF, but decreased miR-29c and increased NOX2 mRNA expression. This unique pattern of mRNA expression may reflect the insidious development of cardiac fibrosis due to subclinical LPS, in contrast to the fibrosis that develops in response to overt diseases, such as myocardial ischemia, heart failure, or hypertrophy. Although mRNA expression of TGF-b did not change, this does not exclude a potential role in mediating LPS-induced cardiac fibrosis since large amounts of latent TGF-b are present in Sildenafil normal hearts, which can be activated by a variety of stimuli in the absence of any change in TGF-b expression. The decrease in miR-29c and increase in NOX2 may be novel mediators of cardiac fibrosis induced by subclinical LPS. The miRs are small, non-coding RNAs that regulate gene expression typically by binding to the 39 untranslated region to inhibit translation and/or decrease stability to increase degradation. There are several hundred miRs in mammals; each miR may have multiple target sites. This network allows small changes in miR levels to regulate several Sildenafil Mesylate cardiovascular processes, including development, hypertrophy, angiogenesis, ion channel function, remodeling, and fibrosis. Individual miRs can be modulated as novel therapeutic targets in cardiovascular diseases. Cardiac fibrosis is associated with downregulation of miR-29, miR-30, miR-101, and miR-133, and upregulation of miR-21. The cardiac fibrosis that develops with decreased miR133 and miR-30c involves CTGF, which did not change with LPS.