细胞因子在心肌重构中的作用

Role of cytokines in myocardiac remodeling

心肌成纤维细胞是心肌合成胶原的主要场所。应激与机械牵张使心肌细胞表达细胞因子。促炎性细胞通过心肌成纤维细胞与心肌细胞的旁分泌作用产生细胞因子,并引起神经-体液变化,通过不同的信号转导通路激活相应基因表达改变引起心肌成纤维细胞的增殖、胶原合成和心肌细胞外基质蛋白的表达,从而参与心肌重构过程。而多种细胞因子均能激活基质金属蛋白酶(MMPs),并通过金属蛋白酶组织抑制剂(TIMPs)共同调控MMPs。心肌重构就是两者之间动态平衡被打破而出现的病理过程。

Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. The triggers of cytokine release in the acute infarction period include mechanical deformation, ischemic stimulus, and cytokine selfamplification pathways. Acutely, the release of tumor necrosis factor, IL-1 and IL-6, transforming growth factor families of cytokines, contribute to survival or deaths of myocytes, modulation of cardiac contractility. This leads to myocardiac remodeling but also initiates the processes of wound healing. Chronically, sustained presence of cytokines leads to myocyte phenotype transition and activation of matrix metalloproteinases. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these processes, producing growth factors and cytokines that act as autocrine and paracrine factors, as well as extracellular matrix proteins and proteinases. This in turn alters the local collagen composition and also the integrins that constitute the interface between myocytes and the matrix.