Increased expression of transforming growth factor-β1 as a stabilizing factor in human atherosclerotic plaques
Increased expression of transforming growth factor-β1 as a stabilizing factor in human atherosclerotic plaques
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DOI：
10.1161/01.str.0000140739.45472.9c
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发表时间：
2004-10-01
期刊：
影响因子：
8.3
通讯作者：
Porreca, E
中科院分区：
文献类型：
--
作者：
Cipollone, F;Fazia, M;Porreca, E
背景和目的-转化生长因子-β（TGF-β）是一种参与血管重塑和动脉粥样硬化形成的生长因子/细胞因子。最近在载脂蛋白E缺陷小鼠中的研究已经证明了TGF-β在维持动脉粥样硬化斑块中炎症和纤维化之间的平衡中的关键作用。此外，TGF-β信号传导的抑制已显示出加速斑块形成及其在小鼠中向不稳定表型的进展。然而，这种机制是否也在人类中起作用仍然是未知的。本研究的目的是表征人颈动脉斑块中TGF-β 1的表达，并将其与炎症浸润的程度和胶原含量与斑块不稳定的临床体征相关联。方法-斑块从接受颈动脉内膜切除术的患者中获得，并根据近期短暂性脑缺血发作或中风的临床证据分为有症状和无症状。通过免疫细胞化学、Western和北方印迹分析噬斑的TGF-β 1表达。免疫细胞化学法用于鉴定CD 68（+）巨噬细胞、CD 3 T淋巴细胞、HLA-DR+细胞和α-平滑肌细胞。前胶原和间质胶原含量进行了分析，通过免疫组化和天狼星红staining. Results-Plaque TGF-β 1 mRNA增加了3倍，在无症状相比，有症状的斑块。无症状组斑块中巨噬细胞和T淋巴细胞数量明显少于有症状组（P < 0.0001）。无症状斑块中TGF-β1蛋白表达增加（P < 0.0001），表明TGF-β1基因转录活跃。免疫组化显示，TGF-β主要表达在斑块肩部，并与斑块前胶原和胶原content.Conclusions的一个可比的增加（P < 0.0001），总之，这项研究表明，高表达的TGF-β1在人类无症状病变，并提供证据，TGF-β1可能在斑块稳定的过程中发挥重要作用。
Background and Purpose - Transforming growth factor-beta (TGF-beta) is a growth factor/cytokine involved in vascular remodeling and atherogenesis. Recent studies in apolipoprotein E-deficient mice have demonstrated a pivotal role of TGF-beta in the maintenance of the balance between inflammation and fibrosis in atherosclerotic plaques. Furthermore, inhibition of TGF-beta signaling has been shown to accelerate plaque formation and its progression toward an unstable phenotype in mice. However, if this mechanism is operative also in humans is still unknown. The aim of this study was to characterize the expression of TGF-beta1 in human carotid plaque and to correlate it with the extent of inflammatory infiltration and collagen content with the clinical signs of plaque instability.Methods - Plaques were obtained from patients undergoing carotid endoarterectomy and divided into symptomatic and asymptomatic according to clinical evidence of recent transient ischemic attack or stroke. Plaques were analyzed for TGF-beta1 expression by Immunocytochemistry, Western, and Northern blotting analysis. Immunocytochemistry was used to identify CD68(+) macrophages, CD3 T lymphocytes, HLA-DR+ cells, and alpha-smooth muscle cells. Procollagen and interstitial collagen content were analyzed by immunohistochemistry and Sirius Red staining, respectively.Results - Plaque TGF-beta1 mRNA was increased up to 3-fold in asymptomatic as compared with symptomatic plaques. Plaques from asymptomatic group had fewer ( P < 0.0001) macrophages and T lymphocytes compared with symptomatic plaques. TGF-β1 gene was transcriptionally active as demonstrated by increased ( P < 0.0001) TGF-beta1 protein expression in asymptomatic plaques. Immunohistochemistry showed that TGF-beta was mainly expressed in plaque shoulder and was associated with a comparable increase ( P < 0.0001) in plaque procollagen and collagen content.Conclusions - In conclusion, this study demonstrates the higher expression of TGF-β1 in human asymptomatic lesions and provides evidence that TGF-β1 may play an important role in the process of plaque stabilization.