Fight Aging!

Atherosclerosis is in part an inflammatory condition, drive by the chronic inflammation of aging. It arises from dysfunction in the macrophage cells responsible for clearing out lipids from blood vessel wall, and inflammatory signaling makes those macrophages less able to perform that maintenance. There are other issues affecting the macrophages, not least of which being that they become overwhelmed by the large amount of cholesterol present in established atherosclerotic lesions, but inflammation is a noteworthy contribution to the problem.

The association between inflammation and atherosclerosis is well established, and mechanistic studies have demonstrated that inflammation is an essential mediator of all stages of atherosclerosis, from initiation to progression and the development of thrombotic complications. Circulating immune cells play a critical role in the build-up of atherosclerotic plaques by adhering to activated endothelium and infiltrating the arterial wall to become lesional cells. This association has led to the study of various anti-inflammatory therapies in the last years.

The bone marrow (BM) is the primary site of haematopoiesis, and the proliferation and migration of haematopoietic progenitors are regulated by various physiological and pathological stimuli. Experimental studies suggest that increased BM haematopoietic activity may be a central link between cardiometabolic risk factors and exacerbated inflammation in atherosclerosis. In mice, hypercholesterolaemia and low HDL-cholesterol levels associated with elevated haematopoietic activity with increased monocytosis and neutrophilia. Hypertension, driven by an overactive sympathetic activation, deteriorates haematopoietic cell niche in the BM which can contribute to atherosclerosis. In humans, it has been suggested that chronic stress accelerates haematopoiesis, giving rise to higher levels of inflammatory cells that might contribute to the atherosclerotic process. In addition, haematopoietic stem cell division rates are increased in subjects with atherosclerosis, and it has been suggested that the haematopoietic system might be chronically affected in these subjects.

However, human data to support this association are sparse. Our purpose was to study the association between cardiovascular risk factors, BM activation, and subclinical atherosclerosis. Whole body vascular 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) was performed in 745 apparently healthy individuals (median age 50.5) from the Progression of Early Subclinical Atherosclerosis (PESA) study. Bone marrow activation (defined as BM 18F-FDG uptake above the median maximal standardized uptake value) was assessed. Systemic inflammation was indexed from circulating biomarkers.

Bone marrow activation was significantly associated with high arterial metabolic activity (18F-FDG uptake). The co-occurrence of BM activation and arterial 18F-FDG uptake was associated with more advanced atherosclerosis, i.e. plaque presence and burden.

Link: https://doi.org/10.1093/eurheartj/ehac102