Swell, or Not Too Swell: Cytokines Regulate Arterial Aneurysm Formation  Peter Libby, Amélie Vromman  Immunity  Volume 47, Issue 5, Pages 814-816 (November 2017) DOI: 10.1016/j.immuni.2017.11.011 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Intersections of Innate Immunity and Extracellular Matrix Metabolism in Arterial Aneurysm Formation This drawing depicts an aortic aneurysm. Arterial smooth muscle cells (shown in the exploded view) comprise the major cell type of the aortic wall. Transforming growth factor β (TGF-β) signaling involves Smad4. Da Ros et al. (2017) show that selective loss of function of Smad4 in smooth muscle cells leads to dysregulated metabolism of the key arterial extracellular matrix molecules: interstitial collagens and elastin. These structural perturbations change the biomechanics of the arterial wall in a manner that favors swelling or aneurysm formation. Smooth muscle cells with Smad4 loss of function also overexpress the pro-inflammatory cytokine interleukin-1β (IL-1β). IL-1β, in turn, augments the production of the mononuclear phagocyte chemoattractant MCP-1 (also known as CCL2). The leukocytes recruited as a consequence localize in and around the aortic wall, and the consequent inflammatory response aggravates aneurysm formation. Blocking IL-1β may thus forestall the arterial swelling involved in the pathogenesis of aortic aneurysms. Immunity 2017 47, 814-816DOI: (10.1016/j.immuni.2017.11.011) Copyright © 2017 Elsevier Inc. Terms and Conditions