Serum rantes, transforming growth factor-β1 and interleukin-6 levels correlate with cardiac muscle fibrosis in patients with aortic valve stenosis

J Physiol Pharmacol. 2018 Aug;69(4). doi: 10.26402/jpp.2018.4.12. Epub 2018 Dec 9.

Abstract

Regulated on Activation Normal T Expressed and Secreted (RANTES) chemokine is involved in the initiation of inflammation and immune-cell recruitment. Interleukin -6 (IL-6) is used as a general index of severity of the chronic inflammatory process. Finally, transforming growth factor-β (TGF-β) is an immune biomarker potentially involved in the regulation of valve fibrosis and calcification. The aim of this study was to analyze selected biomarkers associated with the different stages of immune-pathogenesis in aortic stenosis. Forty consecutive patients with moderate to severe aortic stenosis (AS) and without previous myocardial infarction history were included in the study and divided into two groups. Two imaging techniques, echocardiography and magnetic resonance, were used to estimate the degree of AS and left ventricular muscle function. Inflammatory biomarker serum levels including CCL5/RANTES, IL-6, and TGF-β1 were determined based on ELISA measurements. Mean levels of RANTES, IL-6, and TGF-β1 did not significantly differ between both groups. A negative correlation was found between RANTES serum level and left ventricle (LV) mass as assessed by MRI (r = -0.3358, P = 0.0341). A positive correlation (r = 0.3283, P = 0.0387) was found between IL-6 serum levels and LV mass as measured by MRI. In addition, a positive correlation (r = 0.6803, P = 0.01) was seen between IL-6 serum levels and LV muscle mass with positive late gadolinium enhancement (LGE). There was a positive correlation between TGF-β1 serum level and ejection fraction as measured by echocardiography (r = 0.3217, P = 0.043). The relationship between selected inflammatory biomarkers, LV ejection fraction, LV mass, and LV muscle mass with LGE appeared to be independent of valvular pathobiologic process severity, as we did not observe differences in IL-6, RANTES, or TGF-β1 between groups differing in severity. On the contrary, these markers appear to be linked to myocardial function and remodeling, which may provide valuable insights into the pathobiology of AS and provide a basis for future detection strategies of AS.

MeSH terms

  • Aged
  • Aortic Valve Stenosis* / blood
  • Aortic Valve Stenosis* / diagnostic imaging
  • Aortic Valve Stenosis* / pathology
  • Aortic Valve Stenosis* / physiopathology
  • Chemokine CCL5 / blood*
  • Echocardiography
  • Female
  • Fibrosis
  • Heart / diagnostic imaging
  • Heart / physiopathology
  • Humans
  • Interleukin-6 / blood*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myocardium / pathology*
  • Transforming Growth Factor beta1 / blood*
  • Ventricular Function, Left

Substances

  • CCL5 protein, human
  • Chemokine CCL5
  • IL6 protein, human
  • Interleukin-6
  • TGFB1 protein, human
  • Transforming Growth Factor beta1