Research Article: CD40L promotes development of acute aortic dissection via induction of inflammation and impairment of endothelial cell function

Date Published: March 04, 2018

Publisher: Impact Journals

Author(s): Lu Han, Lu Dai, Yuan-Fei Zhao, Hai-Yang Li, Ou Liu, Feng Lan, Wen-Jian Jiang, Hong-Jia Zhang.

http://doi.org/10.18632/aging.101394

Abstract

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.

Partial Text

Acute aortic dissection (AAD) accounts for a substantial part of deaths from aortic diseases [1]. Type A AAD is the most complicated form according to Stanford classification, which is characterized by abrupt onset, rapid progression and poor prognosis. Type A AAD has a mortality of 50% within the first 48 hours and 90% within 1 month if not operated. However, cumulative evidence has proved that surgery can reduce 1-month mortality to 30% or even lower [2]. Hence, a biomarker which is sensitive and specific for diagnosis or a therapeutic target for delaying development of AAD is of great importance. Elucidation of the risk factors and underlying pathological mechanisms associated with the disease will help us achieve that goal.

AAD is reported to be one of the most fatal cardiovascular disease [13–15]. Thus, rapid diagnosis and effective treatment is essential. Computed Tomography Angiography (CTA) is known to be the gold standard for diagnosis. However, it is not practical and cheap to perform CTA to every patient complaining with chest pain. A biomarker with high sensitivity and specialty that can warn clinicians of AAD is of great importance. Until now, many biomarkers have been tested [16]. Of them all, only d-dimer has a clinically relevant role in the setting of suspected aortic dissection. In our current experiment, we have elucidated that serum CD40L was significantly higher in type A AAD patients, providing a potential biomarker for AAD diagnosis [17]. However, we did not test CD40L level in type B AAD. The sensitivity and specialty of CD40L in diagnosing AAD remain to be demonstrated.

CD40L induces endothelial cells dysfunction through pro-inflammatory effect and further promote AAD development. Thus, CD40L is a potential biomarker for diagnosis and medical treatment to reduce the risk of AAD.

 

Source:

http://doi.org/10.18632/aging.101394

 

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