Blocking Compensatory Matrix Cross-Linking Accelerates ThoracicAortopathy in a Mouse Model of Marfan Syndrome
Mechanical homeostasis plays a central role in promoting and preserving optimal structure and function in the adult aorta. Although pathogenic variants can compromise homeostatic processes, it appears that intramural cells yet attempt to compensate for some genetically induced changes. In particular, lysyl oxidase is higher in the adult Marfan aorta compared with the age-matched control aorta.…
In a study involving a mouse model of Marfan syndrome, researchers found that blocking lysyl oxidase can accelerate the progression of thoracic aortopathy. Lysyl oxidase is typically higher in the adult Marfan aorta compared to a control aorta. When induced hypertension was introduced to adult Fbn1C1041G/+ Marfan syndrome mice, blocking lysyl oxidase resulted in a significant worsening of the aortic condition.
This led to aneurysmal dilatations, dissection, and rupture, with many mice dying prematurely. The deposition and cross-linking of fibrillar collagens, which are extracellular matrix constituents, can act as a protective mechanism against severe disease in the Marfan aorta. The findings suggest that it is crucial to prevent compromising new collagen deposition clinically, and that strategies to enhance collagen cross-linking could potentially be beneficial.
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