2 research outputs found
Agingârelated carcinoembryonic antigenârelated cell adhesion molecule 1 signaling promotes vascular dysfunction
Aging is an independent risk factor for cardiovascular diseases and therefore of particular interest for the prevention of cardiovascular events. However, the mechanisms underlying vascular aging are not well understood. Since carcinoembryonic antigenârelated cell adhesion molecule 1 (CEACAM1) is crucially involved in vascular homeostasis, we sought to identify the role of CEACAM1 in vascular aging. Using human internal thoracic artery and murine aorta, we show that CEACAM1 is upregulated in the course of vascular aging. Further analyses demonstrated that TNFâα is CEACAM1âdependently upregulated in the aging vasculature. Vice versa, TNFâα induces CEACAM1 expression. This results in a feedâforward loop in the aging vasculature that maintains a chronic proâinflammatory milieu. Furthermore, we demonstrate that ageâassociated vascular alterations, that is, increased oxidative stress and vascular fibrosis, due to increased medial collagen deposition crucially depend on the presence of CEACAM1. Additionally, ageâdependent upregulation of vascular CEACAM1 expression contributes to endothelial barrier impairment, putatively via increased VEGF/VEGFRâ2 signaling. Consequently, agingârelated upregulation of vascular CEACAM1 expression results in endothelial dysfunction that may promote atherosclerotic plaque formation in the presence of additional risk factors. Our data suggest that CEACAM1 might represent an attractive target in order to delay physiological aging and therefore the transition to vascular disorders such as atherosclerosis