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2016 ; 7
(50
): 83588-83600
Nephropedia Template TP
Feng W
; Zhang K
; Liu Y
; Chen J
; Cai Q
; Zhang Y
; Wang M
; Wang J
; Huang H
Oncotarget
2016[Dec]; 7
(50
): 83588-83600
PMID27835878
show ga
Vascular calcification (VC) is a significant risk factor for cardiovascular
morbidity and mortality. We recently reported that apocynin had benefits for
preventing cardiovascular diseases. However, whether apocynin could attenuate VC
is unknown. Here, we investigated the role of apocynin in VC and its underlying
mechanisms. 163 participants with high or normal ankle-brachial index (ABI) were
enrolled in this study for analyzing the demographic and biochemical data. In
vitro, vascular smooth muscle cells (VSMCs) were exposed to calcification medium
containing b-glycerophosphate and angiotensin II (Ang II) for 24 hours. The
results showed that serum level of Ang II was significantly increased in patients
with high ABI (P<0.05). In cultured VSMCs, Ang II significantly exacerbated
osteogenic switching. The expression of osteogenic phenotype markers, including
bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2)
and osteopontin (OPN), were significantly upregulated, whereas contractile
markers expression, including alpha smooth muscle actin (a-SMA) and smooth muscle
22 alpha (SM22a) were simultaneously downregulated. However, these effects were
greatly attenuated by apocynin. Apocynin enhanced expression of a-SMA by 5.3%,
and reduced expression of BMP2, Runx2, OPN by 3.37%, 0.61% and 3.07%,
respectively. Furthermore, extracellular signal-regulated kinase 1/2 (ERK1/2)
phosphorylation was upregulated by Ang II, and this effect was also reversed by
apocynin. Intriguingly, pretreatment with U0126, an inhibitor of ERK1/2, had
similar effects with apocynin. Apocynin may act as a novel molecular candidate to
protect against VSMCs osteogenic switching through suppressing ERK1/2 pathway.
|Acetophenones/*pharmacology
[MESH]
|Aged
[MESH]
|Angiotensin II/*pharmacology
[MESH]
|Animals
[MESH]
|Ankle Brachial Index
[MESH]
|Case-Control Studies
[MESH]
|Cells, Cultured
[MESH]
|Female
[MESH]
|Gene Expression Regulation
[MESH]
|Humans
[MESH]
|Male
[MESH]
|Middle Aged
[MESH]
|Mitogen-Activated Protein Kinase 1/*metabolism
[MESH]
|Mitogen-Activated Protein Kinase 3/*metabolism
[MESH]