Abstract
Inflammation of the arterial wall is critical to atherosclerosis pathogenesis. The switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells is essential in the exacerbation of vascular inflammation. Platonin, a cyanine photosensitizing dye, exhibits protective effects in sepsis, trauma, and acute ischemic stroke through its anti-inflammatory capacity in macrophages. The present study investigated the effects and underlying mechanisms of platonin in inflammatory VSMCs. Pretreatment with platonin suppressed the expression of inducible nitric oxide synthetase and mature interleukin-1β but not that of monocyte chemoattractant protein-1 (MCP-1) in VSMCs stimulated by a combination of lipopolysaccharide and interferon-γ (LPS/IFN-γ). Furthermore, platonin inhibited LPS/IFN-γ-induced Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation though the direct reduction of p65Ser536 phosphorylation but not the restoration of Inhibitor of nuclear factor kappa B (IκBα) degradation in VSMCs. However, platonin inhibited Oxidized low-density lipoprotein (ox-LDL)-induced MCP-1 production, possibly through the attenuation of Activator protein 1 (AP-1) binding activity and C-Jun N-terminal kinases ½ (JNK1/2) phosphorylation. Platonin also lowered lipid drop accumulation in VSMCs in Oil red O staining assay. The results collectively indicated that platonin has a vascular protective property with potent anti-inflammatory effects in VSMCs. In conclusion, platonin should be a potential for treating vascular inflammatory diseases such as atherosclerosis.
Highlights
Chronic inflammation of the arterial wall contributes critically to the formation of atherosclerosis [1]
LPS/IFN-γ-induced monocyte chemoattractant protein-1 (MCP-1) production in vascular smooth muscle cells (VSMCs) was unaffected by the incubation with platonin (Figure 1C(c))
We uncovered that treatment by platonin can reduce VSMC proliferation and attenuate macrophage activation [30]
Summary
Chronic inflammation of the arterial wall contributes critically to the formation of atherosclerosis [1]. Atherosclerosis features gradual lipids and accumulation of immune cells in the arterial intima, which can lead to acute clinical outcomes including myocardial infarction and ischemic stroke [2]. Lipid deposition at specific arterial wall sites initiates atheroma pathogenesis. The intimal layer undergoes multiple stages of inflammation, necrosis, fibrosis, and calcification and results in plaque formation [3]. The formation of cholesterol-laden macrophage-derived foam cells is critical in these stages [4]. Foam cells have lower mobility and produce proinflammatory cytokines and chemokines to recruit additional monocytes, T cells, and neutrophils, amplifying
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