CID seminar: A high salt diet promotes atherosclerosis by altering haematopoiesis, 22 May

12-1pm, 22 May, TRF seminar room 1

Presented by Associate Professor Andrew J Murphy, CSL Centenary Fellow, Baker Heart and Diabetes Institute

Western diets typically contain high levels of salt (NaCl), which is linked to an increase in all-cause mortality¹, primarily due to cardiovascular disease (CVD). The relationship between a high salt diet (HSD) and CVD has generally been attributed to hypertension, however this association remains controversial and is not necessarily exclusive. Here we show that HSD can promote an unstable atherosclerotic lesion due to effects on haematopoiesis that enhances lipid-loaded macrophages in the plaque. Indeed, increased circulating monocytes are a causal and independent risk-factor for CVD. Mechanistically, mice fed a HSD displayed monocytosis, driven by haematopoietic stem and progenitor cell (HSPC) mobilisation and extramedullary myelopoiesis in the spleen. This process was initiated by enhanced T_H17 maturation, which promoted osteoclastogenesis in the bone marrow. The enhanced osteoclasts degraded the HSPC endosteal niche and decreased osteoblast-lineage cells, the combined effects of which liberated HSPCs into the circulation. Targeting T_H17 maturation or preserving the endosteal niche, prevented HSPC mobilisation and monocytosis, resulting in smaller atherosclerotic lesions. Our results reveal an immune-driven mechanism for HSD-accelerated CVD, independent of hypertension.

Associate Professor Andrew Murphy heads of the Haematopoiesis and Leukocyte Biology laboratory and the Division of Immunometabolism at the Baker Heart Research Institute. He is a NHMRC Career Development Fellow and National Heart Foundation Future Leader Fellow, recipient of a CSL Centenary Award. Andrew completed is PhD in 2008 in Prof Jaye Chin-Dusting’s laboratory at the Baker and postdoc’d in Prof. Alan Tall’s group at Columbia University. In 2013 he returned to Australia to begin his own group. His work largely focuses on how inflammatory diseases associated with cardiovascular disease, including diabetes, obesity and rheumatoid arthritis cause the overproduction of innate immune cells and how this contributes to atherogenesis or impaired lesion regression. Furthermore, his laboratory studies fundamental biological process regulating haematopoiesis. He has published a number of manuscripts in leading journals including Nature Medicine, Cell Stem Cell, Cell Metabolism and the JCI. He currently holds 2 NHMRC project grants and an ASTAR-NHMRC obesity grant.