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Modulation of Neuropeptide‐Y receptor expression by IGF‐1 and atheroma‐associated cytokines in carotid plaques of symptomatic and asymptomatic patients
Author(s) -
Pankajakshan Divya,
Jia Guanghong,
Pipinos Iraklis,
Agrawal Devendra
Publication year - 2010
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.24.1_supplement.1028.2
Subject(s) - neuropeptide y receptor , medicine , endocrinology , receptor , inflammation , tumor necrosis factor alpha , stimulation , asymptomatic , receptor expression , atheroma , proinflammatory cytokine , biology , neuropeptide
Neuropeptide‐Y (NPY) is involved in the induction of immune‐mediated inflammation. But, its role in atherosclerotic plaques is unknown. Here, we examined NPY‐receptor(R) expression in the presence of IGF‐1 and TNF‐α in plaque smooth muscle cells (pSMCs) of symptomatic(S) and asymptomatic(AS) patients with carotid stenosis. IGF‐1 increased NPY‐Y1 and NPY‐Y5 expression in S (1.5 and 1.2‐fold) and AS pSMCs (2 and 1.5‐fold, respectively). TNF‐α significantly decreased NPY‐Y1R (10‐fold) in S with no change in AS pSMCs. NPY‐Y5R expression decreased significantly in both S and AS pSMCs by TNF‐α. The combined stimulation of the cells with IGF‐1 and TNF‐α increased NPY‐Y1 expression by 1.2‐fold in AS pSMCs but no effects in S pSMCs. In both S and AS pSMCs, IGF‐1 increased NPY‐Y5 expression, but the effect of IGF‐1 in the presence TNF‐α was abolished. IGF‐1 increased (80%) NPY‐Y2 receptor expression in AS pSMCs, but had no significant effect in S pSMCs. NPY‐Y2 expression was higher in AS (2.5‐fold) and S pSMCs (3.5‐fold) upon TNF‐α stimulation than respective controls. Thus, IGF‐1 and TNF‐α differentially modulate NPY‐Y1, ‐Y2 and ‐Y5 receptor expression in AS and S pSMCs. A balance between the inflammatory cytokines and IGF‐1 level at the plaque milieu is critical in determining SMC proliferation or apoptosis at the site of fibrous cap leading to the plaque stability/instability in symptomatic patients with carotid stenosis. (Supported by NIH R01HL073349)