Batlle M, Pérez-Villa F, Lázaro A, García-Pras E, Vallejos I, Sionis A, Castel M A, Roig E
Institut Clínic del Tòrax, Hospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Transplant Proc. 2009 Jul-Aug;41(6):2231-3. doi: 10.1016/j.transproceed.2009.06.009.
Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor-beta1 (TGF-beta1). Analyses using genetically modified mice suggested that TSP-1 may play a protective role to prevent infiltration and tissue remodeling responses after myocardial infarction. The expression levels of TSP-1 and their putative role in ventricular remodeling have not been determined in patients with heart failure (HF).
We analyzed the expression of TSP-1 and TGF-beta1 mRNA in myocardial biopsies from 34 subjects with end-stage HF undergoing heart transplantation and 13 healthy controls from heart donors. Among total RNA extracted from the left ventricle, 1 microg was retrotranscribed and mRNA expression levels were quantified by real-time polymerase chain reaction (PCR).
The mean age of subjects was 54 +/- 2 years; mean ejection fraction, 21 +/- 5%; end-diastolic diameter and end-systolic diameter, 73 +/- 10 and 61 +/- 11 mm, respectively. TSP-1 mRNA expression in ventricular tissue from HF patients was lower (159.04 +/- 14.55 ng-equivalents [ng-equiv]) than in controls (234 +/- 30.66 ng-equiv; P < .05). Tissue from HF subjects also showed lower levels of TGF-beta1 (68.42 +/- 4.36 vs 80.58 +/- 5.26 ng-equiv; P < .05). TSP-1 mRNA levels correlated positively with TGF-beta1 (P = .001; R(2) = .2), and lower TSP-1 mRNA levels were observed with increasing left ventricular diameters.
Patients with end-stage HF show decreased TSP-1 mRNA levels, which agrees with published results showing lower circulating TSP-1. Ventricular dilatation observed in these patients may be related to lower expression of TSP-1. Surprisingly, TGF-beta1 mRNA levels were lower in failing hearts, which suggested that fibrogenesis takes place in earlier phases of HF.
血小板反应蛋白-1（TSP-1）是血管生成的强效抑制剂和组织转化生长因子-β1（TGF-β1）的激活剂。利用基因改造小鼠进行的分析表明，TSP-1可能在预防心肌梗死后的浸润和组织重塑反应中发挥保护作用。心力衰竭（HF）患者中TSP-1的表达水平及其在心室重塑中的假定作用尚未确定。
我们分析了34例接受心脏移植的终末期HF患者心肌活检组织及13例心脏供体健康对照者心肌活检组织中TSP-1和TGF-β1 mRNA的表达。从左心室提取的总RNA中，取1微克进行逆转录，并通过实时聚合酶链反应（PCR）对mRNA表达水平进行定量。
受试者的平均年龄为54±2岁；平均射血分数为21±5%；舒张末期直径和收缩末期直径分别为73±10和61±11毫米。HF患者心室组织中TSP-1 mRNA表达水平（159.04±14.55纳克当量[ng-equiv]）低于对照组（234±30.66 ng-equiv；P<.05）。HF受试者的组织中TGF-β1水平也较低（68.42±4.36对80.58±5.26 ng-equiv；P<.05）。TSP-1 mRNA水平与TGF-β1呈正相关（P=.001；R2=.2），并且随着左心室直径增加，TSP-1 mRNA水平降低。
终末期HF患者的TSP-1 mRNA水平降低，这与已发表的显示循环TSP-1水平较低的结果一致。这些患者中观察到的心室扩张可能与TSP-1表达降低有关。令人惊讶的是，衰竭心脏中TGF-β1 mRNA水平较低，这表明纤维化发生在HF的早期阶段。
