Abstract
BackgroundVascular endothelial growth factor (VEGF) is a signal protein, implicated in various physiological and pathophysiological processes together with other common inflammatory biomarkers. However, their associations have not yet been fully elucidated. In the present study, we investigated associations between VEGF and four specific VEGF mRNA isoforms with levels of 11 inflammation molecules, derived from peripheral blood mononuclear cells (PBMCs) extracts.MethodsHealthy participants from the STANISLAS Family Study (n = 285) were included. Levels of VEGF (four mRNA isoforms and protein levels) and inflammatory molecules (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, INF-γ, TNF-α, MCP-1, EGF) were measured in PBMCs extracts. Multiple regression analyses were performed, adjusted for age and gender.ResultsThe analyses revealed significant associations between VEGF protein levels and levels of IL-4 (β = 0.028, P = 0.013), MCP-1 (β = 0.015, P<0.0001) and EGF (β = 0.017, P<0.0001). Furthermore, mRNA isoform VEGF165 was associated with MCP-1 and IL-1α (P = 0.002 and P = 0.008, respectively); and mRNA isoform VEGF189 was associated with IL-4 and IL-6 (P = 0.019 and P = 0.034, respectively).ConclusionsTo our knowledge, the present study represents the first investigation that successfully demonstrates links between VEGF protein levels and inflammatory molecules levels derived from PBMCs extracts and identifies associations between specific VEGF mRNA isoforms and inflammatory molecules.ImpactThese findings provide novel insights that may assist in the development of new tissue and mRNA isoform specific measurements of VEGF levels, which may positively contribute to predicting the risk of common complex diseases and response of currently used anti-VEGF agents, and developing of novel targeted therapies for VEGF-related pathophysiology.
Highlights
Vascular endothelial growth factor A, VEGF-A, is a multifunctional signal protein, which works as an important regulator of both physiological and pathological angiogenesis and has been related to a variety of pathologies, such as cancer and cardiovascular diseases (CVD) [1]
The analyses revealed significant associations between VEGF protein levels and levels of IL-4 (β = 0.028, P = 0.013), monocyte chemotactic protein 1 (MCP-1) (β = 0.015, P
MRNA isoform VEGF165 was associated with MCP-1 and IL-1α (P = 0.002 and P = 0.008, respectively); and messenger RNA (mRNA) isoform VEGF189 was associated with IL-4 and IL6 (P = 0.019 and P = 0.034, respectively)
Summary
Vascular endothelial growth factor A, VEGF-A (commonly referred as VEGF), is a multifunctional signal protein, which works as an important regulator of both physiological and pathological angiogenesis and has been related to a variety of pathologies, such as cancer and cardiovascular diseases (CVD) [1]. The VEGF gene produces more than 14 messenger RNA (mRNA) isoforms; the most predominant are VEGF121, VEGF145, VEGF165 and VEGF189, denoted by their length (number of amino acids) These isoforms differ in biochemical properties and receptor-binding characteristics that result in different effects on vessel growth [7]. Studies exploring specific VEGF mRNA isoforms for association with inflammatory molecules, intermediate phenotypes and diseases are warranted. Vascular endothelial growth factor (VEGF) is a signal protein, implicated in various physiological and pathophysiological processes together with other common inflammatory biomarkers. Their associations have not yet been fully elucidated. We investigated associations between VEGF and four specific VEGF mRNA isoforms with levels of 11 inflammation molecules, derived from peripheral blood mononuclear cells (PBMCs) extracts.
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