Normal vascular function despite low levels of high-density lipoprotein cholesterol in carriers of the apolipoprotein A-I(Milano) mutant.
BACKGROUND
Carriers of the apolipoprotein A-I(Milano) (apoA-I(M)) mutant have very low plasma high-density lipoprotein cholesterol (HDL-C) levels but do not show any history of premature cardiovascular disease or any evidence of preclinical vascular disease. HDL is believed to prevent the development of vascular dysfunction, which may well contribute to HDL-mediated atheroprotection. Whether the low HDL level of apoA-I(M) carriers is associated with impaired vascular function is presently unknown.


RESULTS
The vascular response to reactive hyperemia, assessed by measuring postischemic increase in forearm arterial compliance, and the plasma concentration of soluble cell adhesion molecules were evaluated in 21 adult apoA-I(M) carriers, 21 age- and gender-matched nonaffected relatives (control subjects), and 21 healthy subjects with low HDL-C (low-HDL subjects). The average plasma HDL-C and apoA-I levels of apoA-I(M) carriers were remarkably lower than those of control subjects and significantly lower than those of low-HDL subjects. The postischemic increase in forearm arterial compliance in the apoA-I(M) carriers was 2-fold greater than in low-HDL subjects and remarkably similar to that of control subjects. Plasma soluble cell adhesion molecule levels were similar in apoA-I(M) carriers and control subjects but were greater in low-HDL subjects. When incubated with endothelial cells, HDL isolated from apoA-I(M) carriers was more effective than HDL from control and low-HDL subjects in stimulating endothelial nitric oxide synthase expression and activation and in downregulating tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule-1.


CONCLUSIONS
Despite their very low HDL levels, apoA-I(M) carriers do not display typical features of impaired vascular function because of an improved activity of apoA-I(M) HDL in maintaining endothelial cell homeostasis.
Gomaraschi
Monica
M
Center Grossi Paoletti, Department of Pharmacological Sciences, University of Milano, Italy.
Baldassarre
Damiano
D
Amato
Mauro
M
Eligini
Sonia
S
Conca
Paola
P
Sirtori
Cesare R
CR
Franceschini
Guido
G
Calabresi
Laura
L
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D002478:Cells, Cultured; D003187:Compliance; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006579:Heterozygote; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000235:genetics; D014664:Vasodilation / Q000502:physiology*
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III