The upregulation of Th1 cells has been suggested to have an essential function in the development of atherosclerosis (AS). Recent studies indicate that miR‐146a is a microRNA specifically and highly expressed in Th1‐driven autoimmune disease. The aim of the study was to investigate the possible mechanisms of the miR‐146a in the onset of acute coronary syndrome (ACS). The results showed that the expression of miR‐146a in peripheral blood mononuclear cells (PBMCs) was significantly increased in patients with ACS. We showed that overexpression of miR‐146a in PBMCs could significantly upregulate the function of Th1 cells. Furthermore, we showed that miR‐146a treatment could modulate the Th1 differentiation through posttranscriptional enhancing the T‐bet pathway in PBMCs. In addition, this study also provided evidence that miR‐146a treatment in vitro could induce the protein expression of TNF‐α, MCP‐1, NF‐κB p65, which are key pro‐inflammatory cytokines and critical transcription factor in AS. In contrast, miR‐146a inhibitor could attenuate these phenomena significantly. The results support the concept that miR‐146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for AS and ACS.

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Fibrin is formed at sites of injury or inflammation and provides the temporary matrix to support vascular cell responses that are also mediated by cytokines including interleukin-1 (IL-1). We have shown previously that fibroblast growth factor 2 (FGF-2) binds with high affinity to fibrin(ogen) . IntroductionHemostatic activation and inflammatory responses both occur at sites of vascular injury, and coordination between these processes is needed for organized cell responses. Fibrinogen and fibrin are prominent at sites of injury, and increased vascular permeability results in movement of fibrinogen into the extracellular space where it may be converted to fibrin. Interactions of inflammatory cells with the endothelium are mediated by fibrinogen that acts as a bridge connecting endothelial cell receptors with inflammatory cells. 1 Degradation products of fibrinogen and fibrin increase vascular permeability and induce chemotaxis at sites of inflammation. 2,3 Fibrin that is formed at sites of injury is critical in hemostasis and also forms the provisional matrix to support cellular processes of repair. In this role, fibrin is not passive, but rather it actively directs cellular processes through specific receptormediated interactions to regulate permeability, 4 endothelial cell adhesion, 5 synthesis and secretion of tissue plasminogen activator and prostacyclin, 6,7 plasminogen activator inhibitor-1, 8 interleukin-8 (IL-8), 9 and von Willebrand factor. 10 Fibrinogen and fibrin are also implicated in the development, progression, and thrombotic complications of atherosclerosis, and they are found in increased amounts in atherosclerotic vessels. 11 The vascular response to injury is also regulated by cytokines including those of the IL-1 family that are important in inflammation. The IL-1 polypeptides are pleiotropic cytokines that affect a wide variety of cells. 12 IL-1␣ and IL-1␤ are 2 members that share many structural features and act on cells through the same receptors. 12 However, they differ in their promoter regions, and IL-1␣ is primarily cell associated, whereas IL-1␤ is extracellular. In endothelial cells, IL-1 induces procoagulant activity, 13 von Willebrand factor release, 14 synthesis of plasminogen activator and plasminogen activator inhibitor-1, 15 and inhibits the thrombomodulin-protein C anticoagulant pathway. 16 On exposure to IL-1, endothelial cells increase synthesis of nitric oxide (NO) 17 and chemoattractant cytokines 18 and express the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) 19 and vascular cell adhesion molecule 1 (VCAM-1). 20 These endothelial cell responses mediate inflammation and also influence hemostasis.We have shown previously that fibrinogen and fibrin bind to the angiogenic growth factors fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF) 21,22 and that fibrinogen potentiates FGF-2 function 23 and provides protection from proteolysis. 24 IL-1␣ and IL-1␤ have structural features similar to FGF-2 including a ␤-barrel structure consisti...

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