Skowasch Dirk, Schrempf Stephanie, Wernert Nicolas, Steinmetz Martin, Jabs Alexander, Tuleta Izabela, Welsch Ulrich, Preusse Claus J, Likungu James A, Welz Armin, Lüderitz Berndt, Bauriedel Gerhard
Department of Cardiology, Heart Center University of Bonn, Bonn, Germany.
Eur Heart J. 2005 Dec;26(23):2576-80. doi: 10.1093/eurheartj/ehi458. Epub 2005 Aug 22.
We assessed aortic valves from patients with non-rheumatic aortic valve stenosis (AS) and with degenerative aortic valve bioprostheses (BP) for the presence of progenitor cell and leukocyte subtype-specific markers.
Diseased valve probes from a total of 87 patients (60 AS and 27 BP) were studied. We assessed presence and localization of endothelial progenitor cells (EPCs: CD34, CD133), dendritic cells (DCs: S100), T-lymphocytes (CD3), and macrophages (CD68) by immunohistochemical and morphometric analyses. In the majority of valves, we detected cell-bound signals of CD34 (48% of AS, 74% of BP, respectively), CD133 (58%/81%), S100 (58%/93%), CD3 (62%/81%), and CD68 (78%/93%). Labelled cells were predominantly localized within the valvular fibrosa. As key results, frequency of EPCs, DCs, macrophages, and lymphocytes was found significantly higher in BP when compared with AS (CD34: 19.2+/-23.2 vs. 5.7+/-13.0%; CD133: 13.7+/-12.4 vs. 5.5+/-8.3%; S100: 15.2+/-12.2 vs. 5.7+/-8.9%; CD3: 3.3+/-2.7 vs. 1.1+/-1.4%; CD68: 35.3+/-26.6 vs. 3.4+/-4.1%; each P<or=0.001).
EPCs and DCs were detected in a large collective of degenerative aortic valves, more frequently in bioprostheses than in native cusps. Aortoluminal presence of these primarily extra-valvular cells co-localized with inflammatory cells is a novel key feature involved in aortic valve degeneration.
我们评估了非风湿性主动脉瓣狭窄(AS)患者和退行性主动脉瓣生物假体(BP)患者的主动脉瓣,以检测祖细胞和白细胞亚型特异性标志物的存在情况。
共研究了87例患者(60例AS和27例BP)的病变瓣膜样本。我们通过免疫组织化学和形态计量分析评估了内皮祖细胞(EPCs:CD34、CD133)、树突状细胞(DCs:S100)、T淋巴细胞(CD3)和巨噬细胞(CD68)的存在及定位。在大多数瓣膜中,我们检测到了CD34(分别为48%的AS和74%的BP)、CD133(58%/81%)、S100(58%/93%)、CD3(62%/81%)和CD68(78%/93%)的细胞结合信号。标记细胞主要定位于瓣膜纤维层。作为关键结果,与AS相比,BP中EPCs、DCs、巨噬细胞和淋巴细胞的频率显著更高(CD34:19.2±23.2对5.7±13.0%;CD133:13.7±12.4对5.5±8.3%;S100:15.2±12.2对5.7±8.9%;CD3:3.3±2.7对1.1±1.4%;CD68:35.3±26.6对3.4±4.1%;各P≤0.001)。
在大量退行性主动脉瓣中检测到了EPCs和DCs,生物假体中的频率高于天然瓣叶。这些主要位于瓣膜外的细胞在主动脉腔内与炎症细胞共定位是主动脉瓣退变的一个新的关键特征。