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Peroxisome proliferator‐activated receptor α activation improves endothelium‐dependent dilation in healthy older men
Author(s) -
Walker Ashley E,
Seibert Sara Marian,
Seals Douglas R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.64
Subject(s) - fenofibrate , medicine , endocrinology , peroxisome proliferator activated receptor , brachial artery , endothelium , receptor , blood pressure
Endothelium‐dependent dilation (EDD) decreases with age. Activation of peroxisome proliferator‐activated receptor α (PPARα) improves EDD in patients with cardiovascular and metabolic diseases. PPARα expression is decreased with aging suggesting a possible role in impaired EDD. We used short‐term administration of fenofibrate (145 mg/day) to activate PPARα while limiting potentially confounding changes in plasma lipids. In 6 healthy older men (65 ± 2 y), mean brachial artery flow‐mediated dilation (FMD) was 24% higher after 2 days (6.2 ± 0.9 vs. 5.0 ± 0.6 %, P=0.18) and 32% higher after 7 days (6.6 ± 0.6 %, P<0.05) of PPARα activation. Endothelium‐independent dilation (sublingual nitroglycerin) did not change. Compared with baseline (105 ± 23 mg/dl), plasma triglycerides were 91 ± 20 mg/dl (P=0.17) and 77 ± 8 mg/dl (P=0.20) after 2 and 7 days of PPARα activation, respectively. Plasma LDL‐cholesterol did not change after 2 days (122 ± 9 mg/dl vs. 121 ± 7 mg/dl, P=0.81), but decreased by ∼10% after 7 days (109 ± 7 mg/dl, P<0.05). In conclusion, short‐term PPARα activation improves brachial artery FMD in healthy older men suggesting that reduced PPARα bioactivity could contribute to impaired EDD with aging. Modest reductions in lipids may or may not play a role in these improvements. Supported by NIH AG013038, AG022241, AG006537, RR00051, and AHA 0715735Z.