TY - JOUR
T1 - Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function
AU - Ellsworth, Darrell L.
AU - Croft, Daniel T.
AU - Weyandt, Jamie
AU - Sturtz, Lori A.
AU - Blackburn, Heather L.
AU - Burke, Amy
AU - Haberkorn, Mary Jane
AU - McDyer, Fionnuala A.
AU - Jellema, Gera L.
AU - Van Laar, Ryan
AU - Mamula, Kimberly A.
AU - Chen, Yaqin
AU - Vernalis, Marina N.
PY - 2014/4
Y1 - 2014/4
N2 - 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. Methods and 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
AB - 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. Methods and 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
KW - Cardiovascular diseases
KW - Gene expression
KW - Lifestyle
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=84903640155&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.113.000121
DO - 10.1161/CIRCGENETICS.113.000121
M3 - Article
C2 - 24563419
AN - SCOPUS:84903640155
SN - 1942-325X
VL - 7
SP - 151
EP - 160
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 2
ER -