Platelet-derived growth factor-AB limits the extent of myocardial infarction in a rat model - Feasibility of restoring impaired angiogenic capacity in the aging heart

Platelet-derived growth factor-AB limits the extent of myocardial infarction in a rat model - Feasibility of restoring impaired angiogenic capacity in the aging heart
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DOI:
10.1161/hc0502.103672
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发表时间:
2002-02-05
期刊:
影响因子:
37.8
通讯作者:
Hong, MK
Hong, MK
中科院分区:
医学1区
文献类型:
--
作者:
Edelberg, JM;Lee, SH;Hong, MK

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背景-与年轻患者相比,老年人心肌梗死的临床结局较差,这可能归因于老年心脏血管生成能力的下降。方法和结果-为了检验心脏微血管内皮细胞的功能表型部分由心肌细胞血小板衍生生长因子(PDGF)-B诱导的旁分泌途径维持的假设,我们用鼠心肌细胞进行了体外研究。这些研究表明,与年轻的内皮细胞不同,当在心肌细胞存在下培养时,衰老心脏的内皮细胞不表达PDGF-B。用离体心脏移植模型评估了这种内皮失调的功能意义,以证明衰老的心脏血管生成活性受到抑制(18月龄小鼠17个同种异体移植物中有2个存活,3月龄小鼠20个中有19个存活; P
Background-Compared with younger patients, myocardial infarction in the elderly has been associated with less favorable clinical outcomes, which may be attributable to a decline in angiogenic capacity in the aging heart.Methods and Results-To test the hypothesis that the functional phenotype of cardiac microvascular endothelial cells is maintained partly by a cardiac myocyte platelet-derived growth factor (PDGF)-B-induced paracrine pathway, we conducted in vitro studies with murine cardiac cells. These studies demonstrated that unlike young endothelial cells, endothelial cells of the aging heart do not express PDGF-B when cultured in the presence of cardiac myocytes. The functional significance of this endothelial dysregulation was assessed with an ex vivo pinnal cardiac allograft model to demonstrate that senescent cardiac angiogenic activity was depressed (2 of 17 allografts were viable in 18-month-old mice versus 19 of 20 in 3-month-old mice; P