Plasma ATP increase is a biomarker of hypertension and triggers low‐grade inflammation through P2X7 receptor

Abstract

Hypertension is accompanied with systemic low‐grade inflammation, and recent evidence shows that inflammation is a driving force of the pathogenesis of hypertension. However, what triggers inflammation in hypertension is unclear. Given that hypertension has sterile inflammation, we examined a panel of danger/damage‐associated molecular patterns (DAMPs) in the blood plasma of mice induced to hypertension by treatment of angiotensin II, L‐NAME or DOCA‐salt. We found that ATP levels consistently rose soon after the onset of hypertension and eventually reached 3 μM. ATP release upregulated CD86 expression in antigen presenting cells (APCs) and heightened immune responses in hypertensive mice. Pharmacological blockade of P2X7 receptor or genetic depletion of P2X7 expression completely abrogated CD86 upregulation, the exaggerated immune responses and blood pressure further increase in hypertensive mice. Unlike the low affinity of ATP to P2X7 in other cells, 3 μM ATP is sufficient to cause Ca2+ inflow in APCs and this is possibly due to their high contents of intracellular lysophospholipids. However, unlike 500 μM ATP, 3 μM ATP did not induce activation of inflammasome, secondary permeability pathway, or cell death in APCs, which indicates that this activation of P2X7 is at low grade. In human, untreated hypertensive patients have substantially elevated plasma ATP levels compared to treated hypertensive patients or normotensive controls. Thus, elevated ATP is a trigger of inflammation and is pathologic in hypertensive disease.Support or Funding InformationNational Natural Science Foundation of China (81670378, 81700365 and 31771266)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.