Key result
Patients with Marfan syndrome had increased pulse wave velocity and MMP-2 levels, but no increase in TGF-β or MMP-9 levels compared with controls.
Why the study?
Aortic dilation, stiffening, and dissection are serious complications in Marfan and Loeys-Dietz syndromes involving abnormal TGF-beta signalling, but the relation of aortic dimensions, stiffness, and biomarker levels is unknown.
Are aortic dimensions, stiffness, and biomarker levels altered in patients with Marfan or Loeys-Dietz syndrome compared to controls?
Cohort (n=131)
Are aortic dimensions, stiffness, and biomarker levels altered in patients with Marfan or Loeys-Dietz syndrome compared to controls?
In patients with Marfan syndrome, aortic stiffness and MMP-2 levels are increased, but TGF-β levels are not, suggesting TGF-β monitoring is not clinically helpful and MMP-2 may represent a different therapeutic target.
MMP-2 elevation may mark aortic stiffness in Marfan syndrome; leaves open TGF-β pathway relevance.
BACKGROUND: Aortic dilation, stiffening, and dissection are common and potentially lethal complications of Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), which involve abnormal transforming growth factor beta (TGF-β) signalling. The relation of aortic dimensions, stiffness, and biomarker levels is unknown. The objective of this study was to measure aortic dimensions, stiffness, TGF-β and matrix metalloproteinase (MMP) levels, and endothelial function in patients with MFS, and to compare TGF-β levels in patients with MFS receiving different therapeutic regimens. METHODS: This was a cohort study of 40 MFS and 4 LDS patients and 87 control participants. Aortic dimension and stiffness indexes, including pulse wave velocity (PWV), were measured using echocardiography and Doppler. Total and free TGF-β and MMP blood levels were measured using Quantikine (R&D Systems, Inc, Minneapolis, MN) and Quanterix (Billerica, MA) kits. Endothelial function was measured using brachial artery flow-mediated dilation. RESULTS: PWV was increased in patients with MFS. There were increased MMP-2 levels in those with MFS but no increase in free or total TGF-β or MMP-9 levels compared with control participants. There was no difference in TGF-β levels between MFS patients receiving no medications, angiotensin receptor blockers, and β-blockers. PWV correlated most strongly with age. Endothelial function showed premature gradual decline in patients with MFS. CONCLUSIONS: Despite the increased PWV, monitoring aortic stiffness or TGF-β levels would not be helpful in patients with MFS. TGF-β levels were not increased and the increased MMP-2 levels suggest consideration of a different therapeutic target.
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Cui et al. (2020) conducted a cohort in Marfan syndrome and Loeys-Dietz syndrome (n=131). Marfan syndrome vs. control participants was evaluated on Aortic dimensions, stiffness, TGF-β and MMP levels, and endothelial function. Patients with Marfan syndrome had increased pulse wave velocity and MMP-2 levels, but no increase in TGF-β or MMP-9 levels compared with controls.
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