Elevated serum levels of proinflammatory cytokines and biomarkers of matrix remodeling in never-treated patients with familial hypercholesterolemia.
BACKGROUND
Familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism, whose origin involves mutations in the gene coding for the low-density lipoprotein receptor protein. Although FH is monogenic, wide variation occurs in the onset and severity of atherosclerosis in these patients.


METHODS
Since data on levels of inflammatory proteins and/or active factors in FH patients who have never received lipid-lowering treatment are lacking, serum levels of MMP-3, active MMP-9 and TIMP-1 as well as pro-inflammatory cytokines (TNF-alpha, IL-18) were determined in never-treated homozygous FH Moroccan patients (n=4) and compared to those of heterozygous FH subjects (n=7) and of healthy control subjects (n=5).


RESULTS
When compared to controls, homozygous FH patients exhibited levels of active MMP-9 and TIMP-1 (p<0.05), and of both high sensitive-CRP and IL-18 which were significantly elevated (p<0.05 and p<0.01, respectively). In heterozygous FH patients, intermediate values between FH homozygotes and healthy controls were observed for these markers, with the exception of MMP-9 activity whose levels were significantly elevated (p<0.05). Multivariate analysis revealed a positive correlation between apolipoprotein B, TIMP-1 and IL-18 levels, and between hs-CRP and IL-18 (p<0.01).


CONCLUSIONS
Although the sample size of this FH group was limited, our data suggest that nontreated homozygous FH patients, and to a lesser degree heterozygous FH patients, exhibit not only a markedly proinflammatory vascular state but also pronounced extracellular matrix remodeling, as reflected by elevated circulating levels of inflammatory cytokines and MMPs.
El Messal
Mariame
M
Faculté des Sciences Aïn Chock, Université Hassan II Aïn Chock, Casablanca, Morocco.
Beaudeux
Jean-Louis
JL
Drissi
Anas
A
Giral
Philippe
P
Chater
Rachid
R
Bruckert
Eric
E
Adlouni
Ahmed
A
Chapman
M John
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000097:blood*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics; D020382:Interleukin-18 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D020382:Interleukin-18; D008055:Lipids; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9