Baylor College of Medicine, One Baylor Plaza, M.S. BCM620, Houston TX, 77030, USA.
J Cardiovasc Transl Res. 2012 Dec;5(6):749-59. doi: 10.1007/s12265-012-9402-7. Epub 2012 Sep 13.
Fibroblasts in the heart play a critical function in the secretion and modulation of extracellular matrix critical for optimal cellular architecture and mechanical stability required for its mechanical function. Fibroblasts are also intimately involved in both adaptive and nonadaptive responses to cardiac injury. Fibroblasts provide the elaboration of extracellular matrix and, as myofibroblasts, are responsible for cross-linking this matrix to form a mechanically stable scar after myocardial infarction. By contrast, during heart failure, fibroblasts secrete extracellular matrix, which manifests itself as excessive interstitial fibrosis that may mechanically limit cardiac function and distort cardiac architecture (adverse remodeling). This review examines the hypothesis that fibroblasts mediating scar formation and fibroblasts mediating interstitial fibrosis arise from different cellular precursors and in response to different autocoidal signaling cascades. We demonstrate that fibroblasts which generate scars arise from endogenous mesenchymal stem cells, whereas those mediating adverse remodeling are of myeloid origin and represent immunoinflammatory dysregulation.
心脏中的成纤维细胞在分泌和调节细胞外基质方面发挥着关键作用，细胞外基质对于维持细胞的最佳结构和机械稳定性至关重要，这是心脏机械功能所必需的。成纤维细胞还密切参与心脏损伤的适应性和非适应性反应。成纤维细胞提供细胞外基质的形成，并作为肌成纤维细胞，负责交联该基质，在心梗后形成机械稳定的瘢痕。相比之下，在心衰期间，成纤维细胞分泌细胞外基质，表现为过度的间质纤维化，可能会机械地限制心脏功能并改变心脏结构（不良重塑）。本文综述了一个假说，即介导瘢痕形成的成纤维细胞和介导间质纤维化的成纤维细胞来自不同的细胞前体，并对不同的自分泌信号级联作出反应。我们证明，产生瘢痕的成纤维细胞来源于内源性间充质干细胞，而介导不良重塑的成纤维细胞来源于骨髓细胞，代表免疫炎症失调。
