VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation.
VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation.
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DOI：
10.1186/1749-8090-6-54
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发表时间：
2011-04-16
影响因子：
1.6
通讯作者：
Chen YJ
中科院分区：
文献类型：
--
作者：
Xu XH;Xu J;Xue L;Cao HL;Liu X;Chen YJ
主动脉瓣狭窄（AS）影响3%的65岁以上的人，导致比其他心脏瓣膜疾病更高的发病率和死亡率。主动脉瓣置换术（AVR）是目前治疗严重症状性AS的唯一治疗选择。然而，对于心室功能差的患者，其死亡率和长期预后并不令人满意，只有少数患者能够承受手术治疗。本课题组前期研究表明，血管内皮生长因子（VEGF）通过经典的VEGF-PI 3 k-Akt和尚不清楚的线粒体抗凋亡通路保护心肌梗死模型的心功能，促进心肌细胞（CM）增殖。本研究旨在测试术前VEGF治疗是否改善AS诱导的心功能不全，以更好地适用于AVR，及其潜在机制。成年雄性小鼠行AS或假手术。2周后，左室游离壁注射腺病毒VEGF（Ad-VEGF）、增强型绿色荧光蛋白（Ad-EGFP）或生理盐水。分娩后两周，通过超声心动图测量所有小鼠并收获用于进一步检测。AS持续4周可引起心肌肥厚和左室功能不全。VEGF治疗增加毛细血管密度，保护线粒体功能，减少CM凋亡，促进CM增殖，并最终保护心脏功能。我们的研究结果表明，VEGF可以修复AS诱导的从代偿性心肌肥厚到心力衰竭的转变。
Aortic stenosis (AS) affects 3 percent of persons older than 65 years and leads to greater morbidity and mortality than other cardiac valve diseases. Surgery with aortic valve replacement (AVR) for severe symptomatic AS is currently the only treatment option. Unfortunately, in patients with poor ventricular function, the mortality and long-term outcome is unsatisfied, and only a minority of these patients could bear surgery. Our previous studies demonstrated that vascular endothelial growth factor (VEGF) protects cardiac function in myocardial infarction model through classic VEGF-PI3k-Akt and unclear mitochondrial anti-apoptosis pathways; promoting cardiomyocyte (CM) proliferation as well. The present study was designed to test whether pre-operative treatment with VEGF improves AS-induced cardiac dysfunction, to be better suitable for AVR, and its potential mechanism. Adult male mice were subjected to AS or sham operation. Two weeks later, adenoviral VEGF (Ad-VEGF), enhanced green fluorescence protein (Ad-EGFP, as a parallel control) or saline was injected into left ventricle free wall. Two weeks after delivery, all mice were measured by echocardiography and harvested for further detection. AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction. VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function. Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.
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