Fritze Olaf, Romero Beatriz, Schleicher Martina, Jacob Marie Paule, Oh Djin-Ye, Starcher Barry, Schenke-Layland Katja, Bujan Julia, Stock Ulrich A
Department of Thoracic and Cardiovascular Surgery, University Hospital Tübingen, Tübingen, Germany.
J Vasc Res. 2012;49(1):77-86. doi: 10.1159/000331278. Epub 2011 Nov 18.
Age-related arterial alterations affecting cells, matrix and biomolecules are the main culprit for initiation and progression of cardiovascular disease. The objective of this study is to gain further insights into the complex mechanism of elastic tissue ageing in human aortic blood vessels.
One hundred and nineteen human aortic tissue samples were collected from adult patients (101 males, 18 females; age 40-86 years) undergoing coronary artery bypass grafting. Overall extracellular matrix architecture was examined by multiphoton laser scanning microscopy and histology. Matrix metalloproteinases 2 and 9, corresponding tissue inhibitors 1 and 2 as well as desmosine were determined. mRNA levels of tropoelastin were assessed by quantitative RT-PCR.
Age-related destruction of the vascular elastic laminas as well as a loss of interlamina cross-links were observed by laser scanning microscopy. These results were confirmed by histology indicating increasing interlamina gaps. There were no significant differences in matrix turnover or desmosine content. A steady decrease in tropoelastin mRNA by about 50% per 10 years of age increase was observed.
Our findings indicate that ageing is accompanied by a destruction of the elastic vascular structure. However, tropoelastin expression analysis suggests that elastogenesis occurs throughout life with constantly decreasing levels.
与年龄相关的影响细胞、基质和生物分子的动脉改变是心血管疾病发生和发展的主要原因。本研究的目的是进一步深入了解人类主动脉血管弹性组织老化的复杂机制。
从接受冠状动脉搭桥手术的成年患者(101名男性,18名女性;年龄40 - 86岁)中收集119份人类主动脉组织样本。通过多光子激光扫描显微镜和组织学检查整体细胞外基质结构。测定基质金属蛋白酶2和9、相应的组织抑制剂1和2以及锁链素。通过定量逆转录聚合酶链反应评估原弹性蛋白的mRNA水平。
通过激光扫描显微镜观察到与年龄相关的血管弹性层破坏以及层间交联的丧失。组织学证实了这些结果,表明层间间隙增加。基质周转或锁链素含量没有显著差异。观察到原弹性蛋白mRNA每增加10岁稳定下降约50%。
我们的研究结果表明,衰老伴随着弹性血管结构的破坏。然而,原弹性蛋白表达分析表明,弹性生成在整个生命过程中都在发生,且水平不断下降。