title: Altered PPARγ Coactivator-1 Alpha Expression in Abdominal Aortic Aneurysm: Possible Effects on Mitochondrial Biogenesis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marike
authors.initials: M
authors.lastname: Gabrielson
authors.forename: Emina
authors.initials: E
authors.lastname: Vorkapic
authors.forename: Maggie
authors.initials: M
authors.lastname: Folkesson
authors.forename: Martin
authors.initials: M
authors.lastname: Welander
authors.forename: Andreas
authors.initials: A
authors.lastname: Matussek
authors.forename: Jan
authors.initials: J
authors.lastname: Dimberg
authors.forename: Toste
authors.initials: T
authors.lastname: Länne
authors.forename: Josefin
authors.initials: J
authors.lastname: Skogberg
authors.forename: Dick
authors.initials: D
authors.lastname: Wågsäter
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D050994:Voltage-Dependent Anion Channels; D000804:Angiotensin II; D002950:Citrate (si)-Synthase; D025261:Mitochondrial Proton-Translocating ATPases