Local arterial Tlr2 stimulation induced neointima and atherosclerotic plaque formation in mouse femoral arteries. Tlr2 stimulation may be an important mediator in arterial occlusive disease.

Although the contribution of Wnt signaling in infarct healing is suggested, its exact role after myocardial infarction (MI) still needs to be unraveled. We evaluated the cardiac presence of active Wnt signaling in vivo following MI, and investigated in which cell types active Wnt signaling was present by determining Axin2 promoter-driven LacZ expression. C57BL/6 Axin2-LacZ reporter mice were sacrificed at days 0, 1, 3, 7, 14, and 21 after LAD ligation. Hearts were snap-frozen for immunohistochemistry (IHC) or enzymatically digested to obtain a single cell suspension for flow cytometric analysis. For both FACS and IHC, samples were stained for β-galactosidase and antibodies against Sca-1, CD31, ckit, and CD45. Active Wnt signaling increased markedly in the myocardium, from 7 days post-MI onwards. Using Sca-1 and CD31, to identify progenitor and endothelial cells, a significant increase in LacZ+ cells was found at 7 and 14 days post-MI. LacZ+ cells also increased in the ckit+ and CD45+ cell population. IHC revealed LacZ+ cells co-expressing Sca, CD31, CD45, vWF, and αSMA in the border zone and the infarcted area. Wnt signaling increased significantly after MI in Sca+- and CD31+-expressing cells, suggesting involvement of Wnt signaling in resident Sca+ progenitor cells, as well as endothelial cells. Moreover, active Wnt signaling was present in ckit+ cells, leukocytes, and fibroblast. Given its broad role during the healing phase after cardiac injury, additional research seems warranted before a therapeutic approach on Wnt to enhance cardiac regeneration can be carried out safely.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-010-0100-9) contains supplementary material, which is available to authorized users.

Abstract-Myocardial infarction is commonly complicated by left ventricular remodeling, a process that leads to cardiac dilatation, congestive heart failure and death. The innate immune system plays a pivotal role in the remodeling process via nuclear factor (NF)-B activation. The NF-B transcription factor family includes several subunits (p50, p52, p65, c-Rel, and Rel B) that respond to myocardial ischemia. Key Words: myocardial infarction Ⅲ ischemic heart disease Ⅲ remodeling Ⅲ NF-B Ⅲ wound healing M yocardial infarction (MI) is commonly complicated by maladaptive left ventricular (LV) remodeling, which refers to alterations in LV chamber mass, geometry, and function. 1 Remodeling is a chronic process, mediated by progressive structural changes in cardiomyocytes and the extracellular matrix (ECM), leading to LV dilatation and impaired systolic function, and potentiates the development of ventricular arrhythmias, heart failure, and subsequent cardiovascular mortality. 2-4 Recently, we have shown that deletion of Toll-like receptor 4 limits ventricular remodeling and improves cardiac function after MI, identifying the innate immune system as a major player in the myocardial response to ischemic injury. 5 Toll-like receptors serve as pattern-recognition receptors within the innate immune system and elicit an inflammatory response via nuclear factor (NF)-B.The NF-B/Rel family regulates transcription via binding to a common decameric sequence motif known as the B site. Members of the NF-B family (p50, p52, p65, c-Rel, and Rel B) share a conserved Rel homology domain and form homoor heterodimers (most commonly p50/p65, p50/p50, or p65/ p65) that are located in the cytosol and are bound to inhibitory IB proteins. Activation of NF-B can be triggered by a variety of stimuli including proinflammatory cytokines, oxidative stress, bacterial and viral products, and also ischemia. 6 -9 Activation leads to rapid phosphorylation, ubiquitination, and subsequent degradation of IB-␣. This allows translocation of the dimer into the nucleus, where it can initiate NF-B-dependent transcription of a large and diverse array of target genes that modulate various physiological and pathological processes, including MI.Following MI, activation of NF-B mediates maladaptive LV remodeling and functional deterioration. 10 Blocking of NF-B activity was therefore suggested to be a promising novel approach to prevent adverse LV remodeling following MI. The role of the different NF-B subunits following MI, however, has not been completely clarified thus far. In this study, we investigate the role of the NF-B p50 subunit in LV Original

The acute phase protein haptoglobin is highly expressed in arteries after sustained £ow changes and involved in cell migration and arterial restructuring. In the liver, haptoglobin expression is mainly regulated by interleukin-6 (IL-6). In the artery, shear stress and NO in£uence IL-6 expression. In the present study, we demonstrate that NO synthesis is involved in the regulation of arterial haptoglobin expression after sustained £ow changes. Decreased haptoglobin expression after NO inhibition coincided with decreased IL-6 levels. However, IL-6 knockout mice had normal arterial haptoglobin expression levels after sustained £ow changes suggesting that other mediators may provide compensatory mechanisms for the regulation of arterial haptoglobin expression.