Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

Keustermans GC, Kofink D, Eikendal A, Jager W, Meerding J, Nuboer R, Waltenberger J, Kraaijeveld AO, Jukema JW, Sels JW, Garssen J, Prakken BJ, Asselbergs FW, Kalkhoven E, Hoefer IE, Pasterkamp G, Schipper HS

Abstract

Childhood obesity coincides with increased numbers of circulating classical CD14(++)CD16(-) and intermediate CD14(++)CD16(+) monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.