Circulation. 2009;120:S1048
(Circulation. 2009;120:S1048.)
© 2009 American Heart Association, Inc.
The Pathophysiology of Peripheral Artery Disease
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Abstract 5095: The Role of Circulating Transforming Growth Factor-β in Vascular Ehlers-Danlos Syndrome: Implications for Drug
Therapy
Florian S Schoenhoff
1;
Benjamin F Griswold
2;
Peter Matt
3;
Leslie J Sloper
4;
Michiyo Yamazaki
5;
Olga D Carlson
6;
Harry C Dietz
7;
Jennifer E Van Eyk
7;
Nazli B McDonnell
81 Johns Hopkins Univ, Baltimore, MD
2 National Institutes on Aging, Baltimore, MD
3 Johns Hopkins Univ, Baltimore, MD
4 National Institutes on Aging, Baltimore, MD
5 Johns Hopkins Univ, Baltimore, MD
6 National Institutes on Aging, Baltimore, MD
7 Johns Hopkins Univ, Baltimore, MD
8 National Institutes on Aging, Baltimore, MD
Objective: TGFβ signaling has been shown to play a major role in the pathogenesis of Marfan syndrome (MFS), leading to a novel
treatment strategy through TGFβ inhibition using losartan. We hypothesized that circulating TGFβ levels may be elevated in
disorders that disrupt arterial wall extracellular matrix, such as the vascular form of Ehlers-Danlos syndrome (VEDS).
Patients and Methods: Circulating levels of TGFβ-1 were measured in EDTA plasma of 141 patients with MFS (n=21, mean age 43±16y),
VEDS (n=41, 37±13y) and controls (n=79, 48±13y) using an electrochemoluminescence platform (LLOQ 4±2.6pg/ml).
Results: In keeping with prior work, this study revealed increased circulating TGFβ in patients with MFS compared to control
patients (9.2±1.2ng/ml vs. 2.5±0.4ng/ml, p<0.0001). Remarkably, the levels seen in patients with VEDS were also significantly
higher than controls (8.0±1.0ng/ml vs. 2.5±0.4ng/ml, p<0.0001) and statistically indistinguishable from those seen in MFS
(9.2±1.2ng/ml vs. 8.0±1.0ng/ml, p=0.5). In a bivariate logistic regression model, the odds ratio was 7.5 (p=0.02, CI 1.3–
43.3) when comparing quartiles of TGFβ values in VEDS patients with age, sex and BMI matched controls. There was a non-statistically
significant trend for higher TGFβ levels in patients without cardiovascular medication (MFS, 11.4±3.0ng/ml; VEDS, 8.5±1.3ng/ml)
compared to patients treated with ARBs and/or ACE-Is (MFS, 6.1±1.0ng/ml; VEDS, 4.6±0.8ng/ml), whereas β-blockers appeared
to have some impact on TGFβ levels in MFS (9.0±1.7ng/ml) but not in VEDS patients (8.3±1.8ng/ml). The influence of age on
TGFβ levels in the controls is statistically significant but weak (r=0.3, p=0.007). In the disease groups, TGFβ is inversely
related to age (MFS, r=–0.7, p<0.0001; VEDS, r=–0.1, p=0.6), which is most likely due to ascertainment bias towards a less
severe phenotype in the older patients and longer duration of medical therapy, especially in the MFS population.
Conclusion: Further investigation is warranted to establish the role of TGFβ signaling in the pathogenesis of VEDS. The current
results may help to provide a rationale for the use of TGFβ lowering drug therapy in this patient population as it is emerging
in the MFS patient population.