Expression of cytoskeleton and energetic metabolism-related proteins at human abdominal aortic aneurysm sites.
OBJECTIVE
The purpose of this study was to evaluate the expression of proteins related to cytoskeleton and energetic metabolism at abdominal aortic aneurysm (AAA) sites using proteomics. Several remodeling-related mechanisms have been associated with AAA formation but less is known about the expression of proteins associated with cytoskeleton and energetic metabolism in AAAs.


METHODS
AAA samples (6.73 ± 0.40 cm size) were obtained from 13 patients during elective aneurysm repair. Control abdominal aortic samples were obtained from 12 organ donors. Proteins were analyzed using two-dimensional electrophoresis and mass spectrometry.


RESULTS
The expression of filamin was increased in the AAA site compared to control abdominal aortic samples while microfibril-associated glycoprotein-4 isotype 1, annexin A5 isotype 1, and annexin A2 were reduced compared with control abdominal aortic samples. Reduction in expression level of energetic metabolism-associated proteins such as triosephosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, and cytosolic aldehyde dehydrogenase was also observed in AAAs compared to controls. Reduction of triosephosphate isomerase expression was also observed by Western blot, which was accompanied by diminished triosephosphate isomerase activity. At the AAA site, pyruvate dehydrogenase expression was reduced and the content of both lactate and pyruvate was increased with respect to controls without changes in lactate dehydrogenase activity.


CONCLUSIONS
The present results suggest that an anaerobic metabolic state may be favored further to reduce the expression of cytoskeleton-related proteins. The better knowledge of molecular mechanism involved in AAAs may favor development of new clinical strategies.
Cardiovascular Research Unit of the Cardiology Department, Cardiovascular Institute, Hospital Clínico San Carlos, San Carlos, Madrid, Spain.
Javier
J
Modrego
Antonio J
AJ
López-Farré
Isaac
I
Martínez-López
Miguel
M
Muela
Carlos
C
Macaya
Javier
J
Serrano
Guillermo
G
Moñux
D000368:Aged; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D015153:Blotting, Western; D016022:Case-Control Studies; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry; D008875:Middle Aged; D000072260:RNA Splicing Factors; D012016:Reference Values; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism
D017306:Annexin A2; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D000072260:RNA Splicing Factors; C016598:microfibrillar protein; D007770:L-Lactate Dehydrogenase; D005634:Fructose-Bisphosphate Aldolase; D014305:Triose-Phosphate Isomerase