Aggrecan: a new biomarker for acute type A aortic dissection

Harald Lahm,Sophia Doll,Karl C König,Stefanie A Doppler,Stefan Eichhorn,Martina Dreßen,Adnan Kastrati,Markus Krane,Stefan Holdenrieder,Nicole Beck,Rüdiger Lange,Kathrin Kraehschuetz

doi:10.1038/s41598-021-89653-y

Abstract

Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. Without surgical intervention the usual mortality rate averages between 1 and 2% per hour. Thus, an early diagnosis of ATAAD is of pivotal importance to direct the affected patients to the appropriate treatment. Preceding tests to find an appropriate biomarker showed among others an increased aggrecan (ACAN) mRNA expression in aortic tissue of ATAAD patients. As a consequence, we investigated whether ACAN is a potential biomarker for diagnosing ATAAD. Mean ACAN protein concentration showed a significantly higher plasma concentration in ATAAD patients (38.59 ng/mL, n = 33) compared to plasma of patients with thoracic aortic aneurysms (4.45 ng/mL, n = 13), patients with myocardial infarction (11.77 ng/mL, n = 18) and healthy volunteers (8.05 ng/mL, n = 12). Cardiac enzymes like creatine kinase MB and cardiac troponin T showed no correlation with ACAN levels in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects an optimum discrimination limit of ACAN plasma levels at 14.3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.

Highlights

Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality
ATAAD patients are often hospitalized with concomitant co-morbidities which mask and complicate the diagnosis of A TAAD5, demanding a high specificity next to a high sensitivity for a reliable biomarker
Our data clearly show that ACAN concentrations were significantly increased in plasma of ATAAD patients compared to plasma samples of healthy individuals and patients suffering from different cardiovascular disease

Summary

Introduction

Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity. After onset of symptoms patients suffering from ATAAD have an associated mortality rate of 1–2% per hour during the first 48 h without surgical intervention. This value increases to 80% after 14 days and to 90% after three months[2]. A clear and early diagnosis of ATAAD is crucial for immediate surgical intervention resulting in an improved survival rate for the patient. The establishment of a specific and sensitive blood biomarker for diagnosing ATAAD would be the key to reduce the time period between symptom onset and the essential surgical treatment. Analysis of the proteoglycanome confirmed the presence of ACAN in the normal human aorta and in aortic lesions of ATAAD patients[15]

Methods

Results

Conclusion