Department of Cardiology and Pneumology, Charité, Universititäts-Medizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Germany.
Circ Heart Fail. 2011 Jan;4(1):44-52. doi: 10.1161/CIRCHEARTFAILURE.109.931451. Epub 2010 Nov 12.
The pathophysiology of heart failure with normal ejection fraction (HFNEF) is still under discussion. Here we report the influence of cardiac inflammation on extracellular matrix (ECM) remodeling in patients with HFNEF.
We investigated left ventricular systolic and diastolic function in 20 patients with HFNEF and 8 control patients by conductance catheter methods and echocardiography. Endomyocardial biopsy samples were also obtained, and ECM proteins as well as cardiac inflammatory cells were investigated. Primary human cardiac fibroblasts were outgrown from the endomyocardial biopsy samples to investigate the gene expression of ECM proteins after stimulation with transforming growth factor-β. Diastolic dysfunction was present in the HFNEF patients compared with the control patients. In endomyocardial biopsy samples from HFNEF patients, we found an accumulation of cardiac collagen, which was accompanied by a decrease in the major collagenase system (matrix metalloproteinase-1) in the heart. Moreover, a subset of inflammatory cells, which expressed the profibrotic growth factor transforming growth factor-β, could be documented in the HFNEF patients. Stimulation of primary human cardiac fibroblasts from HFNEF patients with transforming growth factor-β resulted in transdifferentiation of fibroblasts to myofibroblasts, which produced more collagen and decreased the amount of matrix metalloproteinase-1, the major collagenase in the human heart. A positive correlation between cardiac collagen, as well as the amount of inflammatory cells, and diastolic dysfunction was evident and suggests a direct influence of inflammation on fibrosis triggering diastolic dysfunction.
Cardiac inflammation contributes to diastolic dysfunction in HFNEF by triggering the accumulation of ECM.
射血分数正常心力衰竭（HFNEF）的病理生理学仍在讨论中。在这里，我们报告心脏炎症对 HFNEF 患者细胞外基质（ECM）重塑的影响。
我们通过传导导管方法和超声心动图研究了 20 例 HFNEF 患者和 8 例对照患者的左心室收缩和舒张功能。还获得了心内膜心肌活检样本，并研究了 ECM 蛋白和心脏炎性细胞。从心内膜心肌活检样本中分离出原代人心房成纤维细胞，用转化生长因子-β刺激后研究 ECM 蛋白的基因表达。HFNEF 患者的舒张功能障碍与对照患者相比。在 HFNEF 患者的心内膜心肌活检样本中，我们发现心脏胶原的积累，这伴随着心脏中主要胶原酶系统（基质金属蛋白酶-1）的减少。此外，在 HFNEF 患者中可以记录到表达促纤维化生长因子转化生长因子-β的炎性细胞亚群。用转化生长因子-β刺激 HFNEF 患者的原代人心房成纤维细胞导致成纤维细胞向肌成纤维细胞的转分化，肌成纤维细胞产生更多的胶原，减少主要的人心胶原酶基质金属蛋白酶-1的量。心脏胶原和炎性细胞的数量与舒张功能障碍之间存在正相关，表明炎症对纤维化触发舒张功能障碍有直接影响。
心脏炎症通过触发 ECM 的积累导致 HFNEF 的舒张功能障碍。
