thromboplastin and Essential-Hypertension

Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis, leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies, and surgical specimens of abdominal aortic aneurysms (AAAs) from patients with EH were used. Cell-based assays, NETs/human aortic endothelial cell cocultures, and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly diagnosed patients with EH. Stimulation of control neutrophils with plasma from patients with untreated EH generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via an ROS/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced substantially in patients with EH starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAAs. These data reveal the important pathogenic role of an Ang II/ROS/NET/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Aortic Aneurysm, Abdominal; Autophagy; Case-Control Studies; Cells, Cultured; Coculture Techniques; Collagen; Endothelium; Essential Hypertension; Extracellular Traps; Humans; Kidney; Neutrophils; Reactive Oxygen Species; Thrombin; Thromboinflammation; Thromboplastin; Vasoconstrictor Agents

Occlusive renovascular disease and hypertension may progress to CKD. Circulating levels of several biomarkers, including fibroblast growth factor (FGF)-23, Klotho, and soluble urokinase plasminogen activator receptor (suPAR), are altered in patients with CKD, but their role in essential hypertension (EH) and renovascular hypertension (RVH) remains unclear.. Levels of FGF-23, Klotho, suPAR, plasminogen activator inhibitor (PAI)-1, tissue factor, and tissue factor pathway inhibitor (TFI) were measured in the inferior vena cava and renal vein of hypertensive patients with atherosclerotic renal artery stenosis (n=12) or age-matched participants with EH (n=12) and relatively preserved renal function. Single-kidney blood flow was measured to calculate renal release of markers. For control, peripheral vein levels were measured in healthy volunteers (HVs; n=12).. FGF-23 levels did not differ among the groups, whereas Klotho levels were lower in participants with RVH and EH than in HVs, and suPAR levels were elevated in patients with RVH compared with HVs and patients with EH (6.1±1.5 versus 4.4±1.9 and 3.2±1.2 ng/ml, P<0.05). PAI-1 levels were higher in patients with RVH than in patients with EH, but tissue factor and TFI levels were not statistically significantly different. After adjustment for GFR, Klotho levels remained decreased in both RVH and EH, and suPAR and PAI-1 levels remained elevated in RVH. eGFR correlated inversely with systemic and renal vein suPAR levels, and directly with systemic Klotho levels.. Klotho levels are low in hypertensive patients, whereas suPAR and PAI-1 levels are specifically elevated in RVH, correlating with GFR. Klotho, PAI-1, and suPAR may be markers of kidney injury in hypertensive patients.

Topics: Aged; Atherosclerosis; Biomarkers; Cross-Sectional Studies; Essential Hypertension; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Glucuronidase; Humans; Hypertension; Hypertension, Renovascular; Klotho Proteins; Lipoproteins; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Prospective Studies; Receptors, Urokinase Plasminogen Activator; Renal Artery Obstruction; Renal Circulation; Renal Veins; Thromboplastin; Vena Cava, Inferior