Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
PLoS One. 2012;7(12):e52120. doi: 10.1371/journal.pone.0052120. Epub 2012 Dec 20.
Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV) remodeling after myocardial infarction (MI) remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI.
Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate controls (NLC) were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk) 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42) admitted to hospital for percutaneous coronary intervention (PCI) serum-CTGF levels (s-CTGF) were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15.
Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.
心肌 CCN2/CTGF 在各种病因引起的心力衰竭中被诱导产生。然而，其在心肌梗死后左心室（LV）重构的病理生理学中的作用仍未解决。本研究旨在探讨 CTGF 在动物模型和急性 ST 段抬高型心肌梗死患者中的梗死愈合和 LV 重构中的作用。
过表达 CTGF 的转基因小鼠（Tg-CTGF）和非转基因同窝对照（NLC）被用于永久性结扎左前降支冠状动脉。尽管在冠状动脉结扎后 24 小时，Tg-CTGF 和 NLC 小鼠的梗死面积（梗死面积与危险区域之比）相似，但 Tg-CTGF 小鼠的疤痕组织面积较小，心脏肥大程度增加较小，LV 扩张和 LV 功能恶化程度较低，4 周后 MI。Tg-CTGF 小鼠的死亡率也明显降低。与 NLC 小鼠相比，Tg-CTGF 小鼠的远程/梗死周围组织中的白细胞、巨噬细胞和凋亡细胞数量减少。在一组接受经皮冠状动脉介入治疗（PCI）的急性 ST 段抬高型心肌梗死（n=42）患者中，监测血清 CTGF 水平（s-CTGF），并将其与心脏 MRI 评估的梗死面积和 LV 功能相关联。MI 后 s-CTGF 水平的升高与梗死面积减小和 LV 射血分数改善相关，与 CRP 和 GDF-15 水平降低相关。
MI 后心肌 CTGF 活性增加与 LV 重构的减弱和 LV 功能的改善相关，其机制是通过减轻炎症反应和抑制细胞凋亡。
