Monocyte ablation could treat arterial hypertension
MedWire News: Arterial hypertension could be treated by selective ablation of monocytes, early research suggests.
Laboratory studies by German researchers have shown that certain classes of white blood cells are essential mediators of the promotion of arterial hypertension and vascular dysfunction by angiotensin II.
Therefore, ablation of the "pro-inflammatory monocytes" might alleviate high blood pressure, they suggest.
Angiotensin II is "a potent vasoconstrictor" that causes hypertension. It also promotes myelomonocytic cells to infiltrate vessel walls and stimulates the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in both vascular and inflammatory cells.
This is of particular interest because arterial hypertension is the principal correlate of atherosclerosis, other cardiovascular events, and death worldwide.
In addition, it is believed that an imbalance of pro- and anti-oxidant systems are in part responsible for the development of cardiovascular diseases, including hypertension.
To investigate further, Philip Wenzel (University Medical Center of the Johannes Gutenberg University Mainz) and colleagues studied the role of myelomonocytic cells in the development of angiotensin II-induced arterial hypertension in mice.
They explain that myelomonocytic cells "specifically express the major isoform of lysozyme, lysozyme M," which has a demonstrated role in the pathogenesis of atherosclerosis.
Treating mice with angiotensin II 1mg/kg per day for a week increased the number of specific macrophages (CD11b+Gr-1lowF4/80+) and neutrophils (CD11b+Gr-1highF4/80-) in the aorta.
Selective ablation of myelomonocytic cells positive for lysozyme M (LysM+) with low-dose diphtheria toxin reduced the level of circulating monocytes and their infiltration into the vascular wall, which is induced by angiotensin II. By contrast, the number of neutrophils was not reduced.
As well as attenuating blood pressure rises induced by angiotensin II, reduction of LysM+ cells also attenuated dysfunction of vascular endothelium and smooth muscle, vascular superoxide formation, and expression of NADPH oxidase subunits.
In addition, introduction of wild-type CD11b+Gr-1+ monocytes into mutant mice with reduced monocyte levels restored angiotensin II-induced vascular dysfunction, arterial hypertension, and oxidative stress, while introduction of relevant neutrophils and angiotensin II-knockout mice had no such effect.
Wenzel et al write: "Reconstitution of depleted mice with pro-inflammatory CD11b+Gr-1+ monocytes, but not CD11b+Gr-1+ neutrophils, re-establishes the pathophysiological response to [angiotensin] II."
They add, in the journal Circulation: "Selective ablation of pro-inflammatory Gr-1+CD11b+ monocytes might represent a novel therapeutic principle to treat arterial hypertension."
But before such a cell-based, anti-inflammatory therapy for high blood pressure can be developed, characterization of the hypertension-mediating monocytes, their mode of action, and potential targets for therapeutic intervention is needed, the team concludes.
By Josephine McCoan