The Maastricht Acquisition Platform for Studying Mechanisms of Cell-Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease

Authors

Berta H Ganizada
Koen D Reesink
Shaiv Parikh
Mitch J F G Ramaekers
Asim C Akbulut
Pepijn J M H Saraber
Gijs P Debeij
Mumc-Taa Student Team
Armand M Jaminon
Ehsan Natour
Roberto Lorusso
Joachim E Wildberger
Barend Mees
Geert Willem Schurink
Michael J Jacobs
Jack Cleutjens
Ingrid Krapels
Alexander Gombert
Jos G Maessen
Ryan Accord
Tammo Delhaas
Simon Schalla
Leon J Schurgers
Elham Bidar

Publication Date

7-25-2023

Journal

Biomedicines

Abstract

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold ofMoreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue-cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell-matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.

Keywords

aortic dissection, collagen turnover, connective tissue disorder, elastin degradation, mechanobiology, smooth muscle contractility, tissue biomechanics