Abstract
The inflammation process in large vessels involves the up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are also known as the markers of atherosclerosis. We have reported that Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further examined for its potential in preventing atherosclerosis in this study. In particular, the roles of Chlorella 11-peptide in lowering the production of vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied. The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and agarose gel. Results showed that Chlorella 11-peptide significantly suppressed the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP pathway was involved in the inhibitory cause of the peptide. In addition, this peptide was shown to reduce the extent of increased intercellular permeability induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7 cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW-conditioned medium). These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases.
Highlights
Circulating adhesion molecules (CAMs) are proteins expressed by vascular endothelium that are believed to play a role in the initiation of the atherosclerotic process
The most important adhesion molecules involved in atherosclerosis appear to be intercellular cell adhesion molecule-1 (ICAM-1), endothelial cell selectin (E-selectin), and vascular cell adhesion molecule-1 (VCAM-1)
VCAM-1 is a specific marker for advanced atherosclerosis, since it is often expressed in atherosclerotic plaques [5]
Summary
Circulating adhesion molecules (CAMs) are proteins expressed by vascular endothelium that are believed to play a role in the initiation of the atherosclerotic process. E-selectin levels correlate with cardiovascular disease (CVD) risk [3] and have been used successfully to predict the severity of atherosclerosis in patients [4]. Reducing the elevated ET-1 expression and remaining endothelial intercellular permeability to normal has been demonstrated to be an effective approach to block the development of circulatory disorders, including hypertension and atherosclerosis [16]. Since atherosclerosis is known to be associated with an elevated cholesterol and chronic inflammation [21], examination of the relations between adhesion molecules, MCP-1, ET-1, endothelium membrane integrity with Chlorella 11-peptide would help to explore their therapeutic potential on atherosclerosis. The supernatant of LPS-stimulated RAW264.7 culture was added to endothelial cells (SVEC4-10) for stimulation of these cells This is because activation of macrophage produces pro-inflammatory cytokines required for the development of atherosclerosis [22].
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