Lotte C A Stiekema1, Johan G Schnitzler, Matthias Nahrendorf, Erik S G Stroes. 1. aDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands bDepartment of Imaging, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Atherogenesis is the result of a complex interplay between lipids and innate immune cells, which are descendants of upstream progenitors residing in hematopoietic organs. In this review, we will discuss recent advances in the connection between hematopoiesis and atherogenesis. RECENT FINDINGS: The relevance of a neural-hematopoietic axis was recently supported by the demonstration of a correlation between metabolic activity in the amygdala and the bone marrow. During follow-up, both amygdalar and bone marrow activities also predicted cardiovascular risk in patients, lending further support to a connection between neural stress and cardiovascular events mediated via increased hematopoietic activity.In parallel, functional changes in hematopoietic stem cells may also convey cardiovascular risk. In experimental models, knock-out of the ten-eleven translocation 2 (TET2) gene leading to monocyte-macrophage hyperresponsiveness, was associated with accelerated atherogenesis in murine experiments. In humans, whole-exome sequencing reporting on the 'clonal hematopoiesis of indeterminate potential' gene substantiated a two-fold elevated risk for developing coronary heart disease compared with noncarriers. SUMMARY: Recent studies support the relevance of a 'neural-hematopoietic' inflammatory axis and clonal hematopoiesis as drivers of atherogenesis in humans. These data warrant further studies addressing the role of novel 'hematopoietic' targets for the treatment of patients with increased cardiovascular risk.
PURPOSE OF REVIEW: Atherogenesis is the result of a complex interplay between lipids and innate immune cells, which are descendants of upstream progenitors residing in hematopoietic organs. In this review, we will discuss recent advances in the connection between hematopoiesis and atherogenesis. RECENT FINDINGS: The relevance of a neural-hematopoietic axis was recently supported by the demonstration of a correlation between metabolic activity in the amygdala and the bone marrow. During follow-up, both amygdalar and bone marrow activities also predicted cardiovascular risk in patients, lending further support to a connection between neural stress and cardiovascular events mediated via increased hematopoietic activity.In parallel, functional changes in hematopoietic stem cells may also convey cardiovascular risk. In experimental models, knock-out of the ten-eleven translocation 2 (TET2) gene leading to monocyte-macrophage hyperresponsiveness, was associated with accelerated atherogenesis in murine experiments. In humans, whole-exome sequencing reporting on the 'clonal hematopoiesis of indeterminate potential' gene substantiated a two-fold elevated risk for developing coronary heart disease compared with noncarriers. SUMMARY: Recent studies support the relevance of a 'neural-hematopoietic' inflammatory axis and clonal hematopoiesis as drivers of atherogenesis in humans. These data warrant further studies addressing the role of novel 'hematopoietic' targets for the treatment of patients with increased cardiovascular risk.
Authors: Simone L Verweij; Lotte C A Stiekema; Ronak Delewi; Kang H Zheng; Sophie J Bernelot Moens; Jeffrey Kroon; Charlotte I Stroes; Miranda Versloot; Jan J Piek; Hein J Verberne; Erik S G Stroes Journal: Eur J Nucl Med Mol Imaging Date: 2018-05-04 Impact factor: 9.236
Authors: Annas Al-Sharea; Man K S Lee; Alexandra Whillas; Danielle L Michell; Waled A Shihata; Alyce J Nicholls; Olivia D Cooney; Michael J Kraakman; Camilla Bertuzzo Veiga; Ann-Maree Jefferis; Kristy Jackson; Prabhakara R Nagareddy; Gavin Lambert; Connie H Y Wong; Karen L Andrews; Geoff A Head; Jaye Chin-Dusting; Andrew J Murphy Journal: Haematologica Date: 2018-10-25 Impact factor: 9.941