Is Hypertension a Bone Marrow Disease?
Authors: Kim Ramil C. Montaniel, David G. Harrison
Journal: Circulation (2016)

ypertension affects 30% of the population and 70% of elderly adults.Despite its frequency and decades of research, the etiology of most cases of adult hypertension remains undefined.Perturbations of the kidney, the vasculature, and the central nervous system have all been implicated in the pathogenesis of hypertension.As examples, in most cases of adult hypertension, systemic vascular resistance is elevated and vasodilators lower blood pressure, supporting a vascular etiology.Alternatively, renal cross-transplantation studies have shown that hypertension follows the kidney, and in most cases of experimental hypertension, pressure natriuresis is impaired.Likewise, most single-gene mutations that cause hypertension affect sodium transport in the distal nephron.In keeping with a renal etiology, diuretics and sodium restriction are effective in lowering blood pressure.There is ample evidence to suggest a central-neural cause of hypertension.Sympathetic outflow is almost uniformly increased in experimental models of hypertension and in humans with this disease, and renal denervation has been variably reported to reduce blood pressure.Adrenergic receptor antagonists are commonly used to treat hypertension, further supporting a neural etiology.Is there a unifying mechanism that underlies abnormalities of the brain, kidneys, and the vasculature in hypertension?Accumulating evidence shows that immune cells infiltrate these organs in response to hypertensive stimuli, causing their dysfunction and leading to elevated blood pressure and subsequent end-organ damage.Both innate and adaptive immune cells play a key role in this process.Monocyte/macrophages are increased in the kidney and vasculature of animal models of experimental hypertension and in humans with hypertension.Wenzel et al 1 showed that deletion of monocytes/macrophages completely eliminates angiotensin II-induced hypertension and markedly improves vascular function.Monocytes have several fates on tissue entry.One is to become inflammatory macrophages that can generate reactive oxygen species, release cytokines, and produce matrix metalloproteinases.A second fate is to become monocyte-derived dendritic cells (DCs), which present antigen to T cells and guide T cell fate.Kirabo et al 2 recently showed that such DCs play a major role in hypertension.They demonstrated that hypertension is associated with modification of self-proteins in DCs by oxidized lipid products known as isolevuloglandins, which are immunogenic and seem to act as neoantigens.Adoptive transfer of DCs from hypertensive mice predisposes to severe hypertension and promotes inflammation in the recipients.A third fate of monocytes is transformation to fibrocytes, which are fibroblast precursors that secrete collagen, leading to fibrosis.Wu et al 3 showed that these bone marrow-derived cells accumulate in the perivascular space during hypertension and are responsible for aortic stiffening.Closely related to monocytes are microglial cells of the brain.It has recently become evident that these are activated in hypertension and there is an exchange of these cells with circulating monocytoid cells.Interventions that quiesce microglial cells reduce blood pressure. 4 Hypertension a Bone Marrow disease?