Pauschinger M, Knopf D, Petschauer S, Doerner A, Poller W, Schwimmbeck P L, Kühl U, Schultheiss H P
Medical Clinic II, University Hospital Benjamin Franklin, Freie Universität Berlin, Germany.
Circulation. 1999 Jun 1;99(21):2750-6. doi: 10.1161/01.cir.99.21.2750.
It is controversial whether myocardial fibrosis in end-stage dilated cardiomyopathy (DCM) is associated with altered collagen type I/type III (Col I/Col III) ratio.
Patients with DCM (ejection fraction [EF] <50%, n=12) and with mild global left ventricular dysfunction (EF >50%, n=18) were examined. Col I, Col III, and transforming growth factors-beta1 (TGF-beta1) and -beta2 (TGF-beta2) gene expression in endomyocardial biopsies was evaluated by quantitative competitive reverse transcriptase-polymerase chain reaction (qRT-PCR). Collagen content was quantified after picrosirius red and immunohistological staining and by hydroxyproline assay. In patients with EF <50%, there was a pronounced 2- to 6-fold increase of myocardial Col I mRNA abundance (P<0.01), with a corresponding 1.6-fold increase at the protein level versus that found in patients with EF >50%. The Col III mRNA abundance showed a 2.0-fold increase (P<0.04). There was a relevant shift in the Col I/Col III mRNA ratio for DCM patients (Col I/Col III, 8.2) compared with patients with an EF >50% (Col I/Col III, 6. 4). In addition, total collagen content was increased in patients with EF <50% (n=3) (4.3+/-0.1%) compared with patients with EF >50% (n=8) (2.7+/-0.9%) (P<0.004). The biochemically determined ratio of hydroxyproline/total protein (n=12) was correlated to the Col I mRNA abundance (P<0.05, r=0.77). TGF-beta1 and TGF-beta2 showed elevated myocardial mRNA abundances (1- to 7-fold and 4- to 5-fold, respectively) in DCM patients.
Differential increase of Col I and Col III leads to an increased Col I/Col III ratio in DCM myocardium. Because Col I provides substantial tensile strength and stiffness, this may contribute to systolic and in particular diastolic dysfunction in DCM.
终末期扩张型心肌病（DCM）中的心肌纤维化是否与I型/III型胶原（Col I/Col III）比例改变相关仍存在争议。
对DCM患者（射血分数[EF]<50%，n = 12）和轻度左心室整体功能障碍患者（EF>50%，n = 18）进行检查。通过定量竞争性逆转录聚合酶链反应（qRT-PCR）评估心内膜活检组织中Col I、Col III以及转化生长因子-β1（TGF-β1）和-β2（TGF-β2）的基因表达。经苦味酸天狼星红和免疫组织化学染色以及羟脯氨酸测定对胶原含量进行定量分析。在EF<50%的患者中，心肌Col I mRNA丰度显著增加2至6倍（P<0.01），与EF>50%的患者相比，蛋白质水平相应增加1.6倍。Col III mRNA丰度增加2.0倍（P<0.04）。与EF>50%的患者（Col I/Col III，6.4）相比，DCM患者的Col I/Col III mRNA比例发生了显著变化（Col I/Col III，8.2）。此外，EF<50%的患者（n = 3）总胶原含量（4.3±0.1%）高于EF>50%的患者（n = 8）（2.7±0.9%）（P<0.004）。生化测定的羟脯氨酸/总蛋白比例（n = 12）与Col I mRNA丰度相关（P<0.05，r = 0.77）。DCM患者中TGF-β1和TGF-β2的心肌mRNA丰度升高（分别为1至7倍和4至5倍）。
Col I和Col III的差异增加导致DCM心肌中Col I/Col III比例升高。由于Col I提供了显著的抗张强度和硬度，这可能导致DCM患者出现收缩功能障碍，尤其是舒张功能障碍。
