Dabek Jozefa, Mazurek Urszula, Gasior Zbigniew, Wilczok Tadeusz, Kulach Andrzej, Kucia-Kuzma Sylwia
Department of Cardiology, Medical University of Silesia, Ziolowa 47, 40-635 Katowice, Poland.
Int J Cardiol. 2006 Aug 10;111(2):275-9. doi: 10.1016/j.ijcard.2005.10.006. Epub 2005 Nov 22.
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.
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).
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.
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.
近期数据显示，参与急性冠脉综合征（ACS）病理过程的众多促炎和抗炎因子的基因表达发生了改变。转化生长因子β（TGFβ）信号传导参与多种过程。由于其抗炎和抗动脉粥样硬化作用，它对血管的影响似乎具有保护作用。然而，它似乎也参与了诸如新生内膜形成和纤维化等负面影响。本研究的目的是评估ACS患者中编码TGFβ及其受体（I型、II型和III型）的基因表达。
对24例急性冠脉综合征患者（7例不稳定型心绞痛[UA]和17例心肌梗死[MI]）和10例年龄匹配的健康受试者（对照组）进行了研究。为了评估TGFβ及其受体的基因表达，从外周血单个核细胞（PBMC）中提取总mRNA，并通过定量逆转录聚合酶链反应（QRT-PCR）评估mRNA拷贝数。
与对照组相比，MI和UA患者的TGFβ基因表达显著降低（分别为2789±418拷贝/微克对20262±2548拷贝/微克；p<0.001，以及3390±518拷贝/微克对20262±2548拷贝/微克；p<0.001），其I型受体编码基因的转录活性也明显较低（分别为3295±447拷贝/微克对12859±1929拷贝/微克；p<0.001，以及3258±721拷贝/微克对12859±1929拷贝/微克；p<0.01）和II型受体（分别为2364±346拷贝/微克对19003±2357拷贝/微克；p<0.001，以及2680±522拷贝/微克对19003±2357拷贝/微克；p<0.01）。此外，研究组中III型受体的基因表达低于对照组，尽管差异仅在UA组与对照组之间显著。MI患者和UA患者之间研究基因的表达没有差异。
我们的报告表明，ACS患者中TGFβ活性降低至少部分是由于编码TGFβ及其受体的基因转录活性改变，这可能是动脉粥样硬化病变发展的原因。
