Principal Researcher Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Abstract: Atherosclerosis, an age-related disease with metabolic dysfunction and chronic inflammation, remains a major contributor to cardiovascular disease-mediated mortality worldwide. Recent advancements in regenerative medicine have focused on uncovering extrinsic anti-aging factors showing immunomodulation and metabolic homeostasis to mitigate atherosclerotic progression. A potential rejuvenation factor C (PRFC refer as an alias), a member of the IL-6 cytokine family, utilizes gp130 in its receptor complex to mediate anti-inflammatory and metabolic regulatory effects. Considering its rejuvenation potential and anti-inflammatory capacity, we hypothesized that PRFC overexpression could alleviate atherosclerosis and metabolic disorders. To evaluate this hypothesis, LDL receptor knockout (Ldlr-/-) mice, after being treated intravenously with either AAV-Ctrl or AAV-Prfc, were fed a Western diet for 20 weeks. Overexpression of PRFC led to significant metabolic and vascular improvements. By analyzing DEXA and indirect calorimetry, PRFC-overexpressing mice exhibited reduced body weight gain and fat mass and enhanced energy expenditure despite no differences in food intake. Atherosclerotic plaques in the aortic arch and aorta were significantly reduced in PRFC-overexpressing mice compared to controls. PRFC overexpression decreased the expression of senescence-associated secretory phenotype-related genes, including Mmp13 and Spp1, and ameliorated pro-inflammatory biomarkers in plasmas. These findings provide that PRFC is a novel extrinsic anti-aging factor entailing immunomodulation and metabolic homeostasis, suggesting it might be a promising candidate for developing regenerative therapy for age-related diseases, such as atherosclerosis.
Funding Source: This study was supported by the KRIBB Research Initiative Program, by the NST grant (No. GTL24021-100), by the ABC project grant (RS-2024-00433755), by the Basic Science Research Program (NRF-2021R1I1A2056805).
