Open AccessAging‐related carcinoembryonic antigen‐related cell adhesion molecule 1 signaling promotes vascular dysfunction
Author(s) -
Kleefeldt Florian,
Bömmel Heike,
Broede Britta,
Thomsen Michael,
Pfeiffer Verena,
Wörsdörfer Philipp,
Karnati Srikanth,
Wagner Nicole,
Rueckschloss Uwe,
Ergün Süleyman
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13025
Subject(s) - downregulation and upregulation , biology , endothelial dysfunction , cell adhesion molecule , oxidative stress , tumor necrosis factor alpha , vascular disease , vascular remodelling in the embryo , immunology , microbiology and biotechnology , medicine , endocrinology , biochemistry , gene
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 antigen‐related cell adhesion molecule 1 (CEACAM1) is crucially involved in vascular homeostasis, we sought to identify the role of CEACAM 1 in vascular aging. Using human internal thoracic artery and murine aorta, we show that CEACAM 1 is upregulated in the course of vascular aging. Further analyses demonstrated that TNF ‐α is CEACAM 1‐dependently upregulated in the aging vasculature. Vice versa, TNF ‐α induces CEACAM 1 expression. This results in a feed‐forward loop in the aging vasculature that maintains a chronic pro‐inflammatory milieu. Furthermore, we demonstrate that age‐associated vascular alterations, that is, increased oxidative stress and vascular fibrosis, due to increased medial collagen deposition crucially depend on the presence of CEACAM 1. Additionally, age‐dependent upregulation of vascular CEACAM 1 expression contributes to endothelial barrier impairment, putatively via increased VEGF / VEGFR ‐2 signaling. Consequently, aging‐related upregulation of vascular CEACAM 1 expression results in endothelial dysfunction that may promote atherosclerotic plaque formation in the presence of additional risk factors. Our data suggest that CEACAM 1 might represent an attractive target in order to delay physiological aging and therefore the transition to vascular disorders such as atherosclerosis.