Aggrecan: A New Biomarker for Acute Thoracic Aortic Dissection

Objectives: Acute type A aortic dissection (ATAAD) is a life-threatening situation associated with significant morbidity and mortality. After onset of symptoms patients exhibit a subsequent mortality rate of 1 to 2% per hour if no surgical intervention ensues. Hence, an early and unambiguous diagnosis of ATAAD may decrease the time span until surgical intervention which would improve patients´ survival. Therefore, we investigated whether Aggrecan (ACAN) could serve as a reliable biomarker for diagnosing ATAAD.

Methods: Blood samples from ATAAD patients, healthy controls and additional experimental cohorts were collected prior to operation. Samples were centrifuged (10 minutes, 2,000 × g) and plasma was aliquoted and stored at −80°C until further use. ACAN plasma concentration was determined by commercial ELISA. Human biopsies were obtained during surgical procedures, directly snap-frozen and stored in liquid nitrogen. To analyze gene expression in tissues, frozen biopsies were minced, total RNA was extracted, reverse-transcribed into cDNA and relative gene expression was evaluated by qRT-PCR.

Result: Comparison of 16 different human heart regions showed ACAN with high specificity for arterial vessels. Furthermore, ACAN mRNA abundance is highest in aortic tissue from ATAAD patients in comparison to healthy aortic tissue and further investigated tissues. ACAN protein concentration showed a significantly higher concentration (38.59 ng/mL) compared with plasma of patients with aneurysm (4.45 ng/mL), patients with ST-elevation myocardial infarction (11.77 ng/mL) and healthy volunteers (8.05 ng/mL). The evaluated kinetics of ACAN levels remained clearly elevated up to 72 hour after the onset of symptoms. Established clinical biomarkers like creatine kinase MB and cTnT showed values remaining below the established clinical threshold and no correlation with the levels of ACAN in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects revealed an area under the curve of 0.947 and an ACAN concentration of 14.3 ng/mL in plasma as the optimum discrimination limit, resulting in a sensitivity of 97% and a specificity of 81%.

Conclusion: Our data clearly support ACAN as a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.

Publication History

Article published online:
19 February 2021