Research Paper Volume 10, Issue 3 pp 371—385
CD40L promotes development of acute aortic dissection via induction of inflammation and impairment of endothelial cell function
- 1 Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- 2 Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
- 3 Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
- 4 Beijing Lab for Cardiovascular Precision Medicine, Beijing, China
- 5 Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing, China
- 6 Beijing Engineering Research Center for Vascular Prostheses, Beijing, China
received: January 23, 2018 ; accepted: February 23, 2018 ; published: March 4, 2018 ;https://doi.org/10.18632/aging.101394
How to Cite
Copyright: Han et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute aortic dissection is one of the most lethal cardiovascular disease. The major histopathological feature of AAD is medial degradation, especially breakdown of elastin and collagen. However, the underlying mechanism remains a mystery. Platelets expressed CD40 Ligand (CD40L) is recently recognised as a key effector of cardiovascular disease development through its pro-inflammatory effect. To clarify the role of CD40L in AAD, we examined level of CD40L in human blood serum samples and found that it is significantly higher in AAD patients compared with healthy subjects (26.8±5.52 ng/mL versus 13.4±4.00 ng/mL). To further investigate if CD40L is involve in the development of AAD, we applied β-aminopropionitrile (BAPN) induced mouse model of AAD. Consistent with the human data, circulating CD40L in AAD mice much higher than normal mice (148.40±75.96 pg/mL versus 44.09±19.65 pg/mL). Meanwhile, multiple pro-inflammatory chemokines significantly increased in AAD mice. Importantly, the CD40L-/- mice treated with BAPN did not develop these phenotypes. Lastly, we confirmed that endothelial cells migration was significantly inhibited by CD40L, suggesting impaired recovery from intimal injury. In summary, we found that CD40L promoted AAD development through its pro-inflammatory effects and inhibition of endothelial cell function.