Transcriptional activity of genes encoding Transforming Growth Factor beta and its receptors in peripheral blood mononuclear cells from patients with acute coronary syndromes.

Background: Recent data report altered gene expression of numerous pro- and anti-inflammatory factors involved in pathology of acute coronary syndromes (ACS). Transforming growth factor beta (TGFbeta) signaling is engaged in a wide range of processes. Its effect on vessels seems to be protective due to its anti-inflammatory and anti-atherogenic action. However, it also seems to be engaged in such negative effects as neointima formation and fibrosis. The aim of the study was to assess the expression of the genes encoding TGFbeta and its receptors (type I, II, and III) in patients with ACS.
Methods: The study was carried out on 24 patients with acute coronary syndrome (7 with unstable angina [UA] and 17 with myocardial infarction [MI]) and 10 age-matched healthy subjects (control). To evaluate gene expression of TGFbeta and its receptors total mRNA was extracted from peripheral blood mononuclear cells (PBMC) and the number of mRNA copies were assessed by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR).
Results: MI and UA patients demonstrated significantly lower TGFbeta gene expression compared to control (2789+/-418 c/microg vs. 20262+/-2548 c/microg; p<0.001, and 3390+/-518 c/microg vs. 20262+/-2548 c/microg; p<0.001, respectively), as well as noticeably lower transcriptional activity of genes encoding its type I (3295+/-447 c/microg vs. 12859+/-1929 c/microg; p<0.001, and 3258+/-721 c/microg vs. 12859+/-1929 c/microg; p<0.01, respectively) and type II receptors (2364+/-346 c/microg vs. 19003+/-2357 c/microg; p<0.001, and 2680+/-522 c/microg vs. 19003+/-2357 c/microg; p<0.01, respectively). Also, gene expression of the type III receptor was inferior in the studied group compared to the control, although the difference was significant only for the UA group vs. control. Expressions of the studied genes did not differ between patients with MI and those with UA.
Conclusion: Our report shows that the decreased activity of TGFbeta in patients with ACS is at least partly due altered transcriptional activity of genes encoding both TGFbeta and its receptors, what may be responsible for the evolution of atherosclerotic lesions.