Abstract
Benzo[a]pyrene, a ubiquitous environmental pollutant, has been suggested to be capable of initiating and/or accelerating atherosclerosis. Accumulation of vascular smooth muscle cells (VSMCs) in vessel intima is a hallmark of atherosclerosis. Nitric oxide (NO) can suppress VSMCs proliferation and induce VSMCs apoptosis. NO plays a compensatory role in the vascular lesions to reduce proliferation and/or accelerate apoptosis of VSMCs. The aim of this study was to investigate whether benzo[a]pyrene can affect VSMCs growth and apoptosis induced by NO. Benzo[a]pyrene (1–30 μmol/L) did not affect the cell number and cell cycle distribution in VSMCs under serum deprivation condition. Sodium nitroprusside (SNP), a NO donor, decreased cell viability and induced apoptosis in VSMCs. Benzo[a]pyrene significantly suppressed SNP-induced cell viability reduction and apoptosis. VSMCs cultured in conditioned medium from cells treated with benzo[a]pyrene could also prevent SNP-induced apoptosis. Benzo[a]pyrene was capable of inducing the activation of nuclear factor (NF)-κB and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in VSMCs. Both NF-κB inhibitor and p38 MAPK inhibitor significantly reversed the anti-apoptotic effect of benzo[a]pyrene on SNP-treated VSMCs. Incubation of VSMCs with benzo[a]pyrene significantly and dose-dependently increased interleukin (IL)-6 production. A neutralizing antibody to IL-6 effectively reversed the anti-apoptotic effect of benzo[a]pyrene on SNP-treated VSMCs. Taken together, these results demonstrate for the first time that benzo[a]pyrene activates IL-6 induction and protects VSMCs from NO-induced apoptosis. These findings propose a new mechanism for the atherogenic effect of benzo[a]pyrene.
Highlights
Vascular smooth muscle cells (VSMCs) are responsible for the structural characteristics of the vessel wall, which is important in development, growth, remodeling and repair [1,2]
There was no change on total cell number between control and benzo[a]pyrene (1–30 μmol/ L)-treated VSMCs under serum deprivation culture condition (S1A Fig)
We observed the cell cycle distribution in VSMCs under serum-free condition, and confirmed that no change between control and benzo[a]pyrene (10 μmol/L)-treated VSMCs (S1B Fig). These results indicated that benzo[a]pyrene did not cause cell death of VSMCs in serum-free condition
Summary
Vascular smooth muscle cells (VSMCs) are responsible for the structural characteristics of the vessel wall, which is important in development, growth, remodeling and repair [1,2]. Vascular structure and remodeling have been suggested to be determined in large part by a balance between cell growth and cell death by apoptosis [4]. Epidemiological and experimental studies have shown that polycyclic aromatic hydrocarbons (PAHs) are associated with the progression of cardiovascular diseases, including atherosclerosis [5,6]. The most of studies defining the pathology of benzo[a]pyrene in vascular disease have majorly focused on the abnormal regulation of cell growth/proliferation. In addition to changes in the regulation of cell growth, the regulation of cell death by apoptosis may be another important determinant of vessel structure and lesion formation
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