TEDA International Cardiovascular Hospital and The Affiliated Hospital, Hangzhou Normal University, Tianjin and Hangzhou, China.
PLoS One. 2013 Aug 27;8(8):e72111. doi: 10.1371/journal.pone.0072111. eCollection 2013.
Little is known about genetic basis and proteomics in valvular heart disease (VHD) including rheumatic (RVD) and degenerative (DVD) valvular disease. The present proteomic study examined the hypothesis that certain proteins may be associated with the pathological changes in the plasma of VHD patients.
Differential protein analysis in the plasma identified 18 differentially expressed protein spots and 14 corresponding proteins or polypeptides by two-dimensional electrophoresis and mass spectrometry in 120 subjects. Two up-regulated (complement C4A and carbonic anhydrase 1) and three down-regulated proteins (serotransferrin, alpha-1-antichymotrypsin, and vitronectin) were validated by ELISA in enlarging samples. The plasma levels (n = 40 for each) of complement C4A in RVD (715.8±35.6 vs. 594.7±28.2 ng/ml, P = 0.009) and carbonic anhydrase 1 (237.70±15.7 vs. 184.7±10.8 U/L, P = 0.007) in DVD patients were significantly higher and that of serotransferrin (2.36±0.20 vs. 2.93±0.16 mg/ml, P = 0.025) and alpha-1-antichymotrypsin (370.0±13.7 vs. 413.0±11.6 µg/ml, P = 0.019) in RVD patients were significantly lower than those in controls. The plasma vitronectin level in both RVD (281.3±11.0 vs. 323.2±10.0 µg/ml, P = 0.006) and DVD (283.6±11.4 vs. 323.2±10.0 µg/ml, P = 0.011) was significantly lower than those in normal controls.
We have for the first time identified alterations of 14 differential proteins or polypeptides in the plasma of patients with various VHD. The elevation of plasma complement C4A in RVD and carbonic anhydrase 1 in DVD and the decrease of serotransferrin and alpha-1-antichymotrypsin in RVD patients may be useful biomarkers for these valvular diseases. The decreased plasma level of vitronectin - a protein related to the formation of valvular structure - in both RVD and DVD patients might indicate the possible genetic deficiency in these patients.
关于瓣膜性心脏病（VHD）包括风湿性（RVD）和退行性（DVD）瓣膜病的遗传基础和蛋白质组学知之甚少。本蛋白质组学研究检验了以下假设，即某些蛋白质可能与 VHD 患者血浆中的病理变化有关。
通过二维电泳和质谱分析在 120 名受试者中鉴定出 18 个差异表达的蛋白质斑点和 14 个相应的蛋白质或多肽。通过 ELISA 在扩大样本中验证了 2 个上调（补体 C4A 和碳酸酐酶 1）和 3 个下调蛋白（转铁蛋白、α-1-抗糜蛋白酶和纤连蛋白）。RVD（715.8±35.6 vs. 594.7±28.2ng/ml，P=0.009）和 DVD 患者（237.70±15.7 vs. 184.7±10.8U/L，P=0.007）的补体 C4A 和 DVD 患者的血浆水平（每组 n=40）明显升高，而转铁蛋白（2.36±0.20 vs. 2.93±0.16mg/ml，P=0.025）和 α-1-抗糜蛋白酶（370.0±13.7 vs. 413.0±11.6μg/ml，P=0.019）在 RVD 患者中的水平明显低于对照组。RVD（281.3±11.0 vs. 323.2±10.0μg/ml，P=0.006）和 DVD（283.6±11.4 vs. 323.2±10.0μg/ml，P=0.011）中血浆纤连蛋白水平均明显低于正常对照组。
我们首次鉴定出各种 VHD 患者血浆中 14 种差异蛋白或多肽的改变。RVD 中血浆补体 C4A 的升高和 DVD 中碳酸酐酶 1 的升高以及 RVD 患者转铁蛋白和 α-1-抗糜蛋白酶的降低可能是这些瓣膜病的有用生物标志物。RVD 和 DVD 患者血浆中与瓣膜结构形成有关的蛋白纤连蛋白水平降低，可能表明这些患者存在潜在的遗传缺陷。
