Emerging evidence of neutrophil extracellular traps in essential hypertension and target organ damage: pathophysiological insights and therapeutic implications.

Essential hypertension (EH) remains the leading modifiable risk factor for cardiovascular morbidity and mortality, yet even optimally treated patients carry residual cardiovascular risk. Emerging evidence suggests that chronic subclinical inflammation contributes to the pathogenesis of EH, leading to target organ damage. Neutrophil extracellular traps (NETs), which represent networks of decondensed chromatin carrying neutrophil proteins, have recently gained attention as potent drivers of a harmful thromboinflammatory milieu. While NETs are established contributors to atherosclerotic cardiovascular disease, including ischemic stroke, coronary artery disease and heart failure, their role in hypertension has only recently begun to be elucidated. Preclinical studies demonstrate that NETosis may promote endothelial dysfunction, vascular smooth muscle cell proliferation, and blood pressure elevation, while inhibition of NETs formation attenuates these processes. Clinical data, though limited, indicate that untreated hypertensives exhibit higher circulating NETs, linked to enhanced thrombogenicity, adverse vascular remodeling, and potentially to hypertension-mediated organ damage. Furthermore, therapeutic strategies targeting NETs, ranging from conventional immunomodulatory therapies to biologic agents, are under investigation. This review summarizes current knowledge on the role of NETs in the pathophysiology of EH and related cardiovascular diseases, while discussing potential anti-NETotic effects of currently available pharmacological agents. Hypertensive stimuli promote neutrophil extracellular traps (NETs) formation, leading to thromboinflammation, endothelial injury and vascular damage. These processes are involved in the occurrence of hypertension-mediated organ damage and cardiovascular disease, while sustaining elevated blood pressure. Targeting NET formation may interrupt this vicious cycle and reduce residual cardiovascular risk in hypertension. Ang II, angiotensin II; C5a, compliment component 5a; CVD, cardiovascular disease; HMOD, hypertension-mediated organ damage; IL, interleukin; IsoLGs, isolevuglandins; MPO, myeloperoxidase; NE, neutrophil elastase; NET, neutrophil extracellular traps; RAAS, renin-angiotensin-aldosterone system; ROS, reactive oxygen species; TF, tissue factor; TNFα, tumor necrosis factor α; VSMC, vascular smooth muscle cells.