Altered PPAR gamma Coactivator-1 Alpha Expression in Abdominal Aortic Aneurysm: Possible Effects on Mitochondrial Biogenesis
2016 (English)In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 53, no 1-2, 17-26 p.Article in journal (Refereed) Published
Introduction: 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. PPAR gamma coactivator-1 alpha (PGC1 alpha) regulates VSMC migration and matrix formation and is a major inducer of mitochondrial biogenesis and function, including oxidative metabolism. Methods: Protein and gene expression of PGC1 alpha and markers for mitochondria biogenesis and cell type-specificity were analysed in AAA aortas from humans and mice and compared against control aortas. Results: Gene expression of PPARGC1 A was decreased in human AAA and angiotensin (Ang) II-induced AAA in mice when compared to control vessels. However, high expression of PGC1 alpha was detected in regions of neovascularisation in the adventitia layer. In contract, the intima/media layer of AAA vessel exhibited defective mitochondrial biogenesis as indicated by low expression of PPARGC1 A, VDAC, ATP synthase and citrate synthase. Conclusion: 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 PGC1 alpha and mitochondria biogenesis in AAA. (C) 2016 S. Karger AG, Basel
Place, publisher, year, edition, pages
KARGER , 2016. Vol. 53, no 1-2, 17-26 p.
PGC1 alpha; Abdominal aortic aneurysm; Vascular smooth muscle cells; Mitochondrial biogenesis; Neovascularisation
Cardiac and Cardiovascular Systems
IdentifiersURN: urn:nbn:se:liu:diva-132699DOI: 10.1159/000446653ISI: 000386413400002PubMedID: 27344146OAI: oai:DiVA.org:liu-132699DiVA: diva2:1048097