title: Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function.
abstract: BACKGROUND
  Healthy lifestyle changes are thought to mediate cardiovascular disease risk through pathways affecting endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. We examined the effect of a rigorous cardiovascular disease risk reduction program on peripheral blood gene expression profiles in 63 participants and 63 matched controls to characterize molecular responses and identify regulatory pathways important to cardiovascular health.
  
  
  RESULTS
  Dramatic changes in dietary fat intake (-61%; P<0.001 versus controls) and physical fitness (+34%; P<0.001) led to significant improvements in cardiovascular disease risk factors. Analysis of variance with false discovery rate correction for multiple testing (P<0.05) identified 26 genes after 12 weeks and 143 genes after 52 weeks that were differentially expressed from baseline in participants. Controls showed little change in cardiovascular disease risk factors or gene expression. Quantitative reverse transcription polymerase chain reaction validated differential expression for selected transcripts. Lifestyle modification effectively reduced expression of proinflammatory genes associated with neutrophil activation and molecular pathways important to vascular function, including cytokine production, carbohydrate metabolism, and steroid hormones. Prescription medications did not significantly affect changes in gene expression.
  
  
  CONCLUSIONS
  Successful and sustained modulation of gene expression through lifestyle changes may have beneficial effects on the vascular system not apparent from traditional risk factors. Healthy lifestyles may restore homeostasis to the leukocyte transcriptome by downregulating lactoferrin and other genes important in the pathogenesis of atherosclerosis. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01805492.
authors.affiliation: Integrative Cardiac Health Program.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Ellsworth
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Croft
authors.forename: Jamie
authors.initials: J
authors.lastname: Weyandt
authors.forename: Lori A
authors.initials: LA
authors.lastname: Sturtz
authors.forename: Heather L
authors.initials: HL
authors.lastname: Blackburn
authors.forename: Amy
authors.initials: A
authors.lastname: Burke
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Haberkorn
authors.forename: Fionnuala A
authors.initials: FA
authors.lastname: McDyer
authors.forename: Gera L
authors.initials: GL
authors.lastname: Jellema
authors.forename: Ryan
authors.initials: R
authors.lastname: van Laar
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Mamula
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Chen
authors.forename: Marina N
authors.initials: MN
authors.lastname: Vernalis
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002319:Cardiovascular System / Q000503:physiopathology*; D005247:Feeding Behavior; D005260:Female; D015870:Gene Expression; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D010809:Physical Fitness; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
keywords: cardiovascular diseases; gene expression; lifestyle; obesity