Transforming growth factor-ß and inflammation in vascular (Type IV) ehlers-danlos syndrome

Rachel Morissette, Florian Schoenhoff, Zhi Xu, David A. Shilane, Benjamin F. Griswold, Wuyan Chen, Jiandong Yang, Jie Zhu, Justyna Fert-Bober, Leslie Sloper, Jason Lehman, Natalie Commins, Jennifer E. Van Eyk, Nazli B. McDonnell

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Background: Vascular Ehlers-Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene, COL3A1, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments. Methods and Results: We studied inflammatory and transforming growth factor-ß (TGF-ß) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype-phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-ß1, TGF-ß2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-ß2, whereas downstream canonical/noncanonical TGF-ß signaling was not different. Patients with COL3A1 exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity. Conclusions: These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-ß signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-ß1. Finally, we found a novel role for dysregulated TGF-ß2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalCirculation: Cardiovascular Genetics
Issue number1
StatePublished - Feb 2014


  • Aneurysm
  • Biomarkers
  • Ehlers-Danlos syndrome
  • Extracellular matrix
  • Inflammation

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)


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