title: Site-specific atherogenic gene expression correlates with subsequent variable lesion development in coronary and peripheral vasculature.
abstract: OBJECTIVE
  The relationship between specific gene regulation and subsequent development and progression of atherosclerosis is incompletely understood. We hypothesized that genes in the vasculature related to cholesterol metabolism, inflammation, and insulin signaling pathways are differentially regulated in a site-specific and time-dependent manner.
  
  
  RESULTS
  Expression of 59 genes obtained from coronary, carotid, and thoracic aortic arteries were characterized from diabetic (DM)/hypercholesterolemic (HC) swine (n=52) 1, 3, and 6 months after induction. Lesion development in the 3 arterial beds was quantified and characterized at 1, 3, 6, and 9 months. Progressive lesion development was observed in the coronary>thoracic aorta>>carotid arteries. Genes involved in cholesterol metabolism and insulin pathways were upregulated in coronaries>thoracic aortae>carotids. Inflammatory genes were more markedly upregulated in coronary arteries than the other 2 arteries. Genes implicated in plaque instability (eg, matrix metalloproteinase-9, CCL2 and Lp-PLA(2) mRNAs) were only upregulated at 6 months in coronary arteries.
  
  
  CONCLUSIONS
  Variable gene expression, both in regard to the arterial bed and duration of disease, was associated with variable plaque development and progression. These findings may provide further insight into the atherosclerotic process and development of potential therapeutic targets.
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.forename: Lea
authors.initials: L
authors.lastname: Sarov-Blat
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Damir
authors.initials: D
authors.lastname: Hamamdzic
authors.forename: Andrew
authors.initials: A
authors.lastname: Zalewski
authors.forename: Colin
authors.initials: C
authors.lastname: Macphee
authors.forename: Raul
authors.initials: R
authors.lastname: Llano
authors.forename: Dan
authors.initials: D
authors.lastname: Pelchovitz
authors.forename: Sumeet K
authors.initials: SK
authors.lastname: Mainigi
authors.forename: Hashim
authors.initials: H
authors.lastname: Osman
authors.forename: Troy
authors.initials: T
authors.lastname: Hallman
authors.forename: Klaudia
authors.initials: K
authors.lastname: Steplewski
authors.forename: Zachary
authors.initials: Z
authors.lastname: Gertz
authors.forename: Min Min
authors.initials: MM
authors.lastname: Lu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006937:Hypercholesterolemia / Q000150:complications; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013311:Streptozocin; D013552:Swine
chemical_list: D018932:Chemokine CCL2; D007328:Insulin; D013311:Streptozocin; D002784:Cholesterol; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D020780:Matrix Metalloproteinase 9