Role of bone marrow renin-angiotensin system in the pathogenesis of atherosclerosis.
The renin-angiotensin system (RAS) has been considered to be a circulating hormonal system that regulates blood pressure, blood flow, fluid volume and electrolyte balance. A growing body of evidence indicates local effects of an activated RAS, particularly in the cardiac, vascular, and renal systems. It is now well established that RAS, especially angiotensin II (Ang II) and Ang II type 1 receptor (AT1R) pathway, has significant pro-inflammatory actions on the vessel wall, leading to progression of atherosclerosis. Recent reports suggest that an activated RAS has local effects in bone marrow (BM), which contributes to the regulation of normal and malignant hematologic processes. We reported that AT1aR in BM cells participate in the pathogenesis of atherosclerosis by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1aR. These results suggest that blockade of AT1R not only in vascular cells but also in BM could be an important strategy to prevent atherosclerosis. In this review, we overview recent findings on a role of RAS in the pathogenesis of atherosclerosis, and discuss functional contribution of a local RAS in BM to progression and destabilization of atherosclerotic plaque.
Fukuda
Daiju
D
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
Sata
Masataka
M
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology* / Q000503:physiopathology*; D001853:Bone Marrow / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II