Aim: The current study aims to explore the possible molecular mechanism of hyperhomocysteinemia (HHcy) mediated atherosclerosis (AS) and to find an effective intervention method for AS.
Materials and methods: A total of 40 Wistar rats were equalized into four groups: blank control, HHcy, folacin intervention, and lutein intervention groups. HHcy rat models were established. The intervention groups were respectively lavaged with folacin and lutein. Oxidative stress states, the levels of nitric oxide (NO) and endothelin-1 (ET-1), as well as the expression of nuclear factor (NF)-κB p65 and intercellular adhesion molecule (ICAM)-1 were compared.
Results: In the HHcy rats, the activity of serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) significantly decreased, whereas the malondialdehyde content and hydroxyl radical level noticeably increased, indicating that the rats stayed in aggravated oxidative stress states. Lutein intervention inhibited HHcy-induced oxidative stress excitement. In the HHcy rats, the NO level significantly decreased, whereas the ET-1 level significantly increased, indicating that HHcy mediated vascular endothelial dysfunction. Lutein reversed such dysfunction. In the HHcy rats, the mRNA and protein expression of SOD2 and GPX1 in the aortic wall tissue decreased, whereas that of NF-κB p65 and ICAM-1 increased. Lutein significantly upregulated the mRNA and protein expression of SOD2 and GPx1 and downregulated the expression of NF-κB p65 and ICAM-1.
Conclusions: Oxidative stress and inflammation are the important mechanisms of HHcy-mediated AS. In particular, HHcy-induced aggravated oxidative stress may function as the initial AS-mediating mechanism, upregulating the expression of NF-κB p65 and ICAM-1 and thereby becoming associated with AS. Lutein noticeably intervenes in and inhibits Hcy-mediated oxidative stress excitement and downregulates the expression of inflammation-associated informational molecules.