Hypoxia increases placenta growth factor expression in human myocardium and cultured neonatal rat cardiomyocytes.
Hypoxia increases placenta growth factor expression in human myocardium and cultured neonatal rat cardiomyocytes.
复制标题
DOI：
10.1016/j.healun.2008.11.917
复制
发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Torry DS
中科院分区：
文献类型：
--
作者：
Torry RJ;Tomanek RJ;Zheng W;Miller SJ;Labarrere CA;Torry DS
胎盘生长因子（PlGF）在病理性血管生成中起重要作用，被认为是冠状动脉疾病患者的独立生物标志物。然而，关于PlGF在心脏组织中的表达调控知之甚少。我们检测了在正常和异常的人类同种异体心脏移植活检组织以及缺氧或周期性拉伸条件下培养的心肌细胞中PlGF及其受体VEGFR1的表达变化。无纤维蛋白沉积的人类供体心肌和同种异体移植物活检组织表达PlGF和VEGFR1 mRNA。心肌纤维蛋白活检（n= 7），血清心肌肌钙蛋白I滴度升高（p < 0.03）和细胞浸润（p < 0.05）， PlGF mRNA表达量比不含纤维蛋白的同种异体移植物活检（n=11, p < 0.05）高1.6倍。PlGF蛋白定位于心肌细胞、细胞外基质和部分微血管纤维蛋白沉积区。各组间VEGFR1 mRNA表达无差异。培养的新生大鼠心肌细胞在常氧条件下组成性表达PlGF/VEGFR1。缺氧12 h后PlGF表达增加3.88±0.62倍（n = 6, p≤0.05），缺氧24 h后PlGF表达增加3.64±0.41倍（n = 6, p≤0.05）。较短的缺氧时间、缺氧细胞的条件培养基和周期性拉伸没有显著改变PlGF或VEGFR1的表达。体外缺氧可上调心肌细胞PIGF的表达，在心肌损伤的同种异体移植物中其表达显著增加。总之，这些结果提供了重要的时间和空间证据，证明内源性PlGF可以促进心肌缺氧/缺血后的心脏愈合。
Placenta growth factor (PlGF) plays an important role in pathological angiogenesis and is thought to be an independent biomarker in patients with coronary artery disease. However, little is known regarding the regulation of PlGF expression in heart tissue. We determined expression changes in PlGF and its receptor, VEGFR1, in normal and abnormal biopsies from human cardiac allografts and in cardiomyocytes cultured under hypoxia or cyclical stretch conditions. Human donor myocardium and biopsies from allografts without fibrin deposits expressed PlGF and VEGFR1 mRNA. Biopsies (n = 7) with myocardial fibrin, elevated serum cardiac troponin I titers (p < 0.03) and cellular infiltrates (p < 0.05), expressed 1.6-fold more PlGF mRNA than biopsies from allografts without fibrin (n=11; p < 0.05). PlGF protein was localized in cardiomyocytes, extracellular matrix and some microvessels in areas with fibrin deposition. VEGFR1 mRNA expression was not different between groups. Cultured neonatal rat cardiomyocytes constitutively expressed PlGF/VEGFR1 under normoxia. PlGF expression was increased 3.88 ± 0.62 fold after 12 hours (n = 6; p ≤ 0.05) and 3.64 ± 0.41 fold after 24 hours of hypoxia (n = 6; p ≤ 0.05). Shorter periods of hypoxia, conditioned media from hypoxic cells and cyclical stretch did not significantly alter PlGF or VEGFR1 expression. Cardiomyocyte PIGF expression is upregulated by hypoxia in vitro and its expression increases significantly in allografts with myocardial damage. Collectively, these results provide important temporal and spatial evidence that endogenous PlGF could facilitate cardiac healing following myocardial hypoxia/ischemia.