The inflammatory response in myocardial injury, repair, and remodelling.
Citations
1,299 citations
1,266 citations
Cites background from "The inflammatory response in myocar..."
...A study using cardiac magnetic resonance imaging in p50−/− mice demonstrated that leukocyte p50 expression imparts beneficial effects on remodeling after nonreperfused MI, by improving scar stability and matrix remodeling, and attenuating leukocyte infiltration and cytokine expression.106 These results contrasted with prior I/R and permanent ligation studies of p50−/− mice that reported the opposite results,107,108 but were consistent with a more recent study showing no effects of myocardial p50 deficiency on infarct size during ex vivo I/R in the isolated perfused heart when the influence of circulating leukocytes was removed.109 Taken together, although further study is clearly required, the prevailing evidence underscores the importance of subunitspecificity and cellular localization as determinants of NFκB–mediated responses after MI....
[...]
...As discussed in the text, cell-type–specific innate immune signaling can result in distinctive, and sometimes divergent, in vivo physiological responses during acute MI. Schema derived from Mann,13 Newton and Dixit,14 Schroder and Tschopp,18 Chao,76 and Mann83 (Illustration credit: Ben Smith). by guest on N ovem ber 1, 2017 http://circres.ahajournals.org/ D ow nloaded from TLR pathways) to active IL-18 and IL-1β (Figure 2)....
[...]
...Thus, growth differentiation factor-15 loss in mice is associated with accentuated postinfarction inflammation and fatal cardiac rupture after MI.202 In patients with ST-segment– elevation MI, elevated plasma growth differentiation factor-15 levels are associated with increased mortality,203 likely reflecting activation of a protective anti-inflammatory pathway in patients with an accentuated postinfarction inflammatory reaction....
[...]
...Interestingly, S100A1, the S100 protein most abundant in cardiomyocytes, is also released from damaged cardiomyocytes in both humans and mice with acute MI.48 However, rather than promoting generalized inflammation, S100A1 is taken up by endocytosis in adjacent cardiac fibroblasts to transiently activate TLR4-endolysosomal signaling, resulting in an immunomodulatory and antifibrotic phenotype with beneficial effects on post-MI LV remodeling in vivo.48 This suggests that specific DAMPs have unique cell targets and functional roles in the cardiac repair process that can be either pro- or anti-inflammatory....
[...]
...In this regard, a recent study has demonstrated that circulating IL-1β induces the proliferation of bone marrow hematopoietic stem cells after MI, thereby enhancing circulating leukocytes and inflammation in the infarcted heart.127 As another example, the chemokine CXCL12/stromal cell–derived factor-1 may facilitate cardiac repair after MI by promoting homing and survival of stem cells and neovascularization.128,129 Finally, it is important to recognize that the inflammation is a required event for effective tissue repair, and as such suppression of inflammatory activation that is not dysregulated or excessive may not necessarily result in salubrious effects on cardiac remodeling after MI....
[...]
1,260 citations
634 citations
604 citations
References
3,917 citations
2,677 citations
2,305 citations
2,215 citations