促炎细胞因子
肌成纤维细胞
炎症
细胞外基质
纤维化
趋化因子
基质金属蛋白酶
心肌梗塞
医学
肉芽组织
心脏纤维化
伤口愈合
免疫学
细胞生物学
病理
内科学
生物
作者
Frans A. van Nieuwenhoven,Neil A. Turner
标识
DOI:10.1016/j.vph.2012.07.003
摘要
Cardiac fibroblasts (CF) play a pivotal role in the repair and remodeling of the heart that occur following myocardial infarction (MI). The transition through the inflammatory, granulation and maturation phases of infarct healing is driven by cellular responses to local levels of cytokines, chemokines and growth factors that fluctuate in a temporal and spatial manner. In the acute inflammatory phase early after MI, CF contribute to the inflammatory milieu through increased secretion of proinflammatory cytokines and chemokines, and they promote extracellular matrix (ECM) degradation by increasing matrix metalloproteinase (MMP) expression and activity. In the granulation phase, CF migrate into the infarct zone, proliferate and produce MMPs and pro-angiogenic molecules to facilitate revascularization. Fibroblasts also undergo a phenotypic change to become myofibroblasts. In the maturation phase, inflammation is reduced by anti-inflammatory cytokines, and increased levels of profibrotic stimuli induce myofibroblasts to synthesize new ECM to form a scar. The scar is contracted through the mechanical force generated by myofibroblasts, preventing cardiac dilation. In this review we discuss the transition from myocardial inflammation to fibrosis with particular focus on how CF respond to alterations in proinflammatory and profibrotic signals. By furthering our understanding of these events, it is hoped that new therapeutic interventions will be developed that selectively reduce adverse myocardial remodeling post-MI, while sparing essential repair mechanisms.
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