Abstract 15235: Circulating Immune Profile of Aging, a Translational Study on the Role of Growth Differentiation Factor-15 and Monokine Induced by Interferon gamma

• Published in: Circulation (New York, N.Y.) Vol. 140; no. Suppl_1 Suppl 1; p. A15235
• Main Authors: Arthur, Jennifer A, Bouajila, Sara, Amsallem, Myriam, Shen Orr, Shai, Kobayashi, Yukari, Rosenberg-Hasson, Yael, Alpert, Ayelet, Moneghetti, Kegan J, Dekker, Cornelia, Contrepois, Kevin, Martin, Beth A, Kouznetsova, Tatiana, Davis, Mark, Karakikes, Ioannis, Maecker, Holden T, Haddad, Francois
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 19-11-2019
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.15235

IntroductionWhile inflammation is frequently found in elderly individuals, it remains controversial whether healthy aging is associated with an increase in pro-inflammatory markers.ObjectiveTo determine the immune profile associated with aging and identify the endothelial effect of these molecules.MethodsThe study included a first derivation cohort of 102 healthy individuals (age 20-90 yo, mean age 57.4±18.3 years, 55% of females) free of cardiovascular disease, inflammatory condition or cancer. Targeted immune profiling (48-plex Luminex), C-reactive protein, Growth Differentiation Factor-15 (GDF-15), galactin-3 and metabolic profiling with insulin and comprehensive lipid panel was performed. For validation, we profiled an additional cohort of 78 less healthy individuals and applied an in-vitro endothelial cell validation model investigating the effects of immune molecules on aging stressors.ResultsIn the derivation cohort, GDF-15 and Monokine induced by Interferon Gamma (MIG also known as CXCL9) were strongly associated with the cardiovascular parameterspulse wave velocity (PWV) is a marker of arterial stiffness and mitral lateral e’ is a marker of myocardial relaxation.. These cytokines were the most correlated with age (R=0.73 and R=0.59, for PWV and e’, respectively, p<0.001), a finding which was confirmed in the validation cohort. In-vitro treatment with GDF-15 and CXCL9 attenuated the endothelial dysfunction phenotype (i.e. decrease in eNOS and increase in ICAM-1 mRNA endothelial expression) after exposure to IL-1B and oxidative stress.ConclusionsGDF-15 and CXCL9 are strongly correlated with age and have modulating effects on inflammasome or oxidative stress mediated endothelial cells injury.