Preliminary observation of chemokine expression in patients with Stanford type A aortic dissection

doi:10.1016/j.cyto.2019.154920

Cytokine

Volume 127, March 2020, 154920

https://doi.org/10.1016/j.cyto.2019.154920 Get rights and content

Abstract

Stanford type A Aortic dissection (TAAD) is a deadly cardiovascular disease but the relationship between inflammatory cytokines and disease pathogenesis is still unclear. Observation of the changes of different chemokines may help to explore the etiology of TAAD much further. Clinical data was collected from TAAD patients (TAAD group) and healthy controls (HC group) in our institute between October 2013 and December 2014. Blood sample was harvested from each subject of two groups. The expression levels of eighty chemokines were examined by protein array technology. Then we tested the expressions of macrophage inflammatory protein 1β (MIP-1β), epithelial neutrophil activating peptide 78 (ENA-78), interleukin 16 (IL-16), interferon inducible protein 10 (IP-10), and FMS-like tyrosine kinase 3 (Flt-3) ligand by using luminex technology. Osteopontin (OPN) and monocyte chemotaxis protein (MCP) levels were analyzed by ELISA kits. The mean age of TAAD group is 49.9 ± 11.2 and 48.7 ± 9.9 in HC group, respectively. 76.0% of TAAD patients and 72.0% of healthy controls were male. MIP-1β and ENA-78 expression in TAAD group were significantly lower than that in HC group, while significant increasing IL-16 level was found. Plasma levels of OPN in TAAD group increased remarkably compared with HC group, but MCP-1 and MCP-2 expression significantly decreased. No correlation was shown between serum CRP levels and plasma level of these cytokines by using Spearman analysis. ROC analysis showed that OPN could be indicators for TAAD diagnosis with sensitivity of 0.92 and specificity of 0.99. Our results provide a reasonable way to focus on the chemokines in understanding the pathogenesis of human TAAD.

Introduction

Stanford type A Aortic dissection (TAAD) is one of dangerous cardiovascular diseases. Although surgery is considered to be the most effective method to save lives, the outcomes is still worse with high rates of morbidity and mortality. In fact, since victims before hospital admission might not be included in the database, the number of TAAD patients could be more than that we thought before [1]. Further etiological exploration is much necessary so as to reduce the incidence of TAAD and improve the clinical outcome.

Several commonly diseases have been known to be risk factors of aortic dissection such as systemic hypertension, atherosclerosis, genetic and autoimmune disorders [2]. Abnormal inflammatory response and signal pathway widely exist in the pathogenesis of these diseases [3], [4], [5]. Logically speaking, there could be potential relationships between TAAD and inflammatory regulation. Focusing on cytokines expression may help to unveil the concrete formation of TAAD. In the past decade, it had been found that a few proteins were involved in the onset and progression of aortic dissection as inflammatory mediators [6], [7]. However, most of these studies were concentrated on C-reactive protein (CRP), metalloproteinase family and transforming growth factor-beta signal pathway [6], [7], [8]. The expression changes of chemotactic proteins in TAAD patients which might contribute to the formation of dissected vessels were still unclear. Therefore, in this study, we tried to sort out chemokines with abnormal expression by protein microarray and Luminex technique which maybe help to expand key proteins pool concerning the pathogenesis of aortic dissection.

Section snippets

Patient selection

Clinical data was collected from TAAD patients (TAAD group) and healthy controls (HC group) in the Affiliated Drum Tower Hospital of Nanjing University Medical School between October 2013 and December 2014. All the patients without coronary artery disease and degenerative valvular heart disease were included. We ruled out the subjects with connective tissue diseases, autoimmune diseases or organ malperfusion and dysfunction. Healthy controls were all enrolled from medical examination center in

Enrolled subjects

Fifty TAAD patients were eligible for this study. The time from symptoms onset to hospitalization is 5–79 h (average 13.4 ± 12.9 h). This is also the time lag between symptoms onset and blood sampling. Twenty-five healthy controls (HC group) were also included. All TAAD patients underwent surgical treatment and the time from hospitalization to operation is 2–72 h (average 7.9 ± 6.7 h). The mean age of TAAD group is 49.9 ± 11.2 and 48.7 ± 9.9 in HC group, respectively. 76.0% of TAAD patients and

Discussion

Further exploration of the TAAD pathogenesis is vital to reduce the mortality and improve clinical outcomes. Previous studies about TAAD showed that overexpression of MMPs in the media of aortic vessel wall lead to proteins degradation and dysfunction of vascular smooth muscle cells (VSMCs) [8]. The excessive activation of transforming growth factor-β (TGF-β) signaling pathway could result in the abnormal structure of aortic vessel tissue which may promote the initiation and progression of TAAD

Conclusion

Our study found that plasma MIP-1β, ENA-78, MCP-1 and MCP-2 were significantly decreased but OPN and IL-16 were remarkably increased in TAAD patients, suggesting chemokines disorder in the pathogenesis of TAAD. OPN could be used as a biomarker for the diagnosis of TAAD.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

None.

Sources of funding

This study was supported by the Medical Science and Technology Development Foundation, Nanjing Department of Health, China (No. YKK13071), and the National Natural Science Foundation of China (No. 81800408).

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Preliminary observation of chemokine expression in patients with Stanford type A aortic dissection

Abstract

Introduction

Section snippets

Patient selection

Enrolled subjects

Discussion

Conclusion

Declaration of Competing Interest

Acknowledgments

Sources of funding

Clin. Chim. Acta

Cancer Lett.

Ageing Res. Rev.

J. Mol. Cell. Cardiol.

J. Mol. Cell Cardiol.

Atherosclerosis

Aortic dissection

Nat. Rev. Dis. Primers

Predicting death in patients with acute type A aortic dissection

Circulation