Gabrielson Marike, Vorkapic Emina, Folkesson Maggie, Welander Martin, Matussek Andreas, Dimberg Jan, Länne Toste, Skogberg Josefin, Wågsäter Dick
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
J Vasc Res. 2016;53(1-2):17-26. doi: 10.1159/000446653. Epub 2016 Jun 25.
Abdominal aortic aneurysm (AAA) is a complex and deadly vascular disorder. The pathogenesis of AAA includes destruction and phenotypic alterations of the vascular smooth muscle cells (VSMCs) and aortic tissues. PPARγ coactivator-1 alpha (PGC1α) regulates VSMC migration and matrix formation and is a major inducer of mitochondrial biogenesis and function, including oxidative metabolism.
Protein and gene expression of PGC1α and markers for mitochondria biogenesis and cell type-specificity were analysed in AAA aortas from humans and mice and compared against control aortas.
Gene expression of PPARGC1A was decreased in human AAA and angiotensin (Ang) II-induced AAA in mice when compared to control vessels. However, high expression of PGC1α was detected in regions of neovascularisation in the adventitia layer. In contrast, the intima/media layer of AAA vessel exhibited defective mitochondrial biogenesis as indicated by low expression of PPARGC1A, VDAC, ATP synthase and citrate synthase.
Our results suggest that mitochondrial biogenesis is impaired in AAA in synthetic SMCs in the media, with the exception of newly formed supporting vessels in the adventitia where the mitochondrial markers seem to be intact. To our knowledge, this is the first study investigating PGC1α and mitochondria biogenesis in AAA.
腹主动脉瘤（AAA）是一种复杂且致命的血管疾病。AAA的发病机制包括血管平滑肌细胞（VSMC）和主动脉组织的破坏及表型改变。过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC1α）调节VSMC迁移和基质形成，并且是线粒体生物发生和功能（包括氧化代谢）的主要诱导因子。
分析了人类和小鼠AAA主动脉中PGC1α的蛋白质和基因表达以及线粒体生物发生和细胞类型特异性标志物，并与对照主动脉进行比较。
与对照血管相比，人类AAA和小鼠中血管紧张素（Ang）II诱导的AAA中PPARGC1A的基因表达降低。然而，在外膜层新生血管形成区域检测到PGC1α的高表达。相反，AAA血管的内膜/中膜层表现出线粒体生物发生缺陷，这表现为PPARGC1A、电压依赖性阴离子通道（VDAC）、ATP合酶和柠檬酸合酶的低表达。
我们的结果表明，除了外膜中新形成的支持血管中线粒体标志物似乎完整外，AAA中膜合成型平滑肌细胞的线粒体生物发生受损。据我们所知，这是第一项研究AAA中PGC1α和线粒体生物发生的研究。
