Endothelial function in subjects with isolated low HDL cholesterol: role of nitric oxide and circulating progenitor cells.
Epidemiologic studies have shown that a low level of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular diseases. The purpose of this study was to determine the contribution of isolated low HDL cholesterol to endothelial function. Thirty-nine subjects with low HDL cholesterol who had no other cardiovascular risk factors were selected from the 5,417 participants from our population. We evaluated flow-mediated vasodilation (FMD) before and after 4 wk of treatment with the HMG-CoA reductase inhibitor pravastatin in 29 of the 39 subjects with isolated low HDL cholesterol. FMD was lower in the low-HDL-cholesterol group (n = 29) than in the control group (n = 29), whereas NTG-induced vasodilation was similar in the two groups. Pravastatin increased HDL cholesterol, urinary excretion of nitrite/nitrate, circulating levels of progenitor cells, and cell migration response to vascular endothelial growth factor in 15 subjects with low HDL cholesterol but not in 14 placebo control subjects. FMD increased in the pravastatin treatment group but not in the control group. NTG-induced vasodilation was similar before and after 4 wk of treatment in the two groups. Multiple regression analysis revealed that changes in HDL cholesterol, the number of progenitor cells, and migration of progenitor cells were independent predictors of augmentation of FMD with pravastatin. These findings suggest that low HDL cholesterol is an independent risk factor for endothelial dysfunction and that pravastatin improves endothelial function in individuals with isolated low HDL cholesterol through, at least in part, an increase in circulating progenitor cells.
Higashi
Yukihito
Y
Department of Cardiovascular Physiology and Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. yhigashi@hiroshima-u.ac.jp
Matsuoka
Hidehiro
H
Umei
Hidekazu
H
Sugano
Ryo
R
Fujii
Yuichi
Y
Soga
Junko
J
Kihara
Yasuki
Y
Chayama
Kazuaki
K
Imaizumi
Tsutomu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin; D017035:Pravastatin / Q000494:pharmacology*; D012016:Reference Values; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents; D055815:Young Adult
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; D017035:Pravastatin