Blood Plasma TGF- β1 Concentration in Sporadic Dilatative Pathology of Ascending Aorta: More Questions than Answers

Abstract

Transforming growth factor β1 (TGF- β1) is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- β1 levels are associated with Marfan syndrome (MFS) caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- β1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA) and in reference group subjects (n = 212). An initial screening of 212 reference individuals identified TGF- β1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- β1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1–25.3, and median 6.2 ng/ml, range 1.0–33.1, respectively). There is a significant association between TGF-β1 concentration and DPAA (OR 1.084, CI 1.027–1.144, p = 0.004) but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-β1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-β1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-β1 levels with an emphasis on preanalytical phase and the choice of sample.

Blood biomarkers in patients with bicuspid aortic valve disease

“…In addition, we provided reference values for TGF-ß1, based on 85 healthy volunteers without aortic dilatation with an age range from 20 to 50 years. The mean TGF-ß1 levels that we found (11.8 AE 3.2 ng/mL) were both lower [45] or higher [8,9] than in previously published studies. This could possibly be due to differences in affinity of the antibodies in the immunoassays or inclusion of different reference groups (patient without BAV versus local population).…”

“…In older patients with degenerative aortic valve stenosis, higher C-reactive protein (CRP) is associated with more severe aortic stenosis [7], but no evidence is available on aortic valve stenosis in patients with a BAV. Finally transforming growth factor-beta 1 (TGF-ß1) is found to be elevated in blood samples of patients with aortic dilatation or syndromes [8][9][10][11]. Yet, only small numbers ranging between 9 and 30 patients with a BAV were included in these studies.…”

Circulating interleukin-6 (IL-6) levels are associated with aortic dimensions in genetic aortic conditions

“…Plasma IL-6 levels among normal patients have been reported to show a range from 0.014 to 6.7 pg/ml,[ 21 ] and plasma TGF-β1 levels have been reported to show median reference levels of 6.2 (range 1.0–33.1) ng/ml in healthy control subjects. [ 22 ] Plasma MMP-9, TIMP-1 and TIMP-2 levels have been reported to be 107.7±53.96 ng/ml, 250.03±53.96 ng/ml, and 58.79±8.26 ng/ml (mean±SD), respectively. [ 23 ] It is noted that these normal reference values are derived from control groups higher in age than our study population.…”

Plasma for Laboratory Diagnostics

“…There are different tubes for plasma or serum collection (see Figure 2) and sometimes different applications due to the variable pathophysiological effects of platelets and clotting process to be involved for laboratory findings [11] ( Table 2).…”