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.

Essential hypertension (EH) is a principal contributing factor in worldwide cardiovascular disease mortality. Although interventions that minimize environmental risk factors for EH are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic EH risk. In this study, we investigated possible associations between ACE2 polymorphisms and hypertension-related target organ damages in south Xinjiang, China. Four hundred and two hypertensive patients were enrolled as study participants in an EH group, and 233 normotensive individuals were enrolled as control subjects. Participants were recruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Risk genotypes of rs2074192 (TT+CT, OR = 1.72, 95% CI: 1.17-2.53), rs2106809 (TT, OR = 1.71, 95% CI: 1.13-2.58), rs4240157 (CC+CT, OR = 1.99, 95% CI: 1.17-3.41), rs4646155 (TT+CT, OR = 1.94, 95% CI: 1.06-3.54), rs4646188 (TT+CT, OR = 3.25, 95% CI: 1.95-5.41), rs4830542 (CC+CT, OR = 1.88, 95% CI: 1.10-3.23), and rs879922 (CC+CG, OR = 4.86, 95% CI: 2.74-8.64) were associated with EH. Hypertensive patients carrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28-4.39) were associated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157 (OR = 2.62, 95% CI: 1.24-5.54), rs4646155 (OR = 2.44, 95% CI: 1.16-5.10), or rs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03-4.69) were associated with atrial fibrillation (AF), larger left atrial diameter, and higher levels of renin-angiotensin-aldosterone system (RAAS) activation (renin and angiotensin I/II). In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS ≥50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associated with EH- and hypertension-related AF and left atrial remodeling in south Xinjiang, China.

BackgroundCardiovascular benefits by reversing environmental risks factors for essential hypertension (EH) and dyslipidemia could be weaken by high genetic risk. We investigated possible associations between ACE2 polymorphisms and dyslipidemia in patients with EH.MethodsFour hundred and two hypertensive patients were enrolled in an EH group and 233 normotensive individuals were enrolled as control group from the Xinjiang region of China. Fourteen ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry.ResultsParticipants carrying T allele (TT + CT) of rs2074192 (P = 0.006), rs4646155 (P = 0.030) and rs4646188 (P ConclusionThe ACE2 rs4646188 variant may be a potential and optimal genetic susceptibility marker for EH, dyslipidemia and its related ischemic stroke.

MicroRNA-155 (miR-155) has emerged as a pivotal regulator in the development of hypertension. However, its role in the mechanism underlying hypertension remains incompletely defined, especially in vascular inflammation and dysfunction. This review synthesizes and evaluates the published literature on the role of miR-155 in the regulation of inflammation, endothelial dysfunction (ED), and vascular smooth muscle cells (VSMCs) function in essential hypertension (EH). We evaluated experimental and clinical studies investigating the expression patterns, molecular targets, and pathways involving miR-155 in endothelial cells (EC), VSMCs in hypertensive conditions. MiR-155 is consistently upregulated in the circulating and tissue of hypertensive models and patients. MiR-155 intensifies inflammation by suppressing endothelial nitric oxide synthase (eNOS) production, enhancing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and promoting pro-inflammatory cytokine expression. In EC, miR-155 directly targets eNOS, leading to impaired nitric oxide (NO) bioavailability and vasodilation by inhibiting the phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K/Akt) pathway. miR-155 modulates the renin-angiotensin-aldosterone system (RAAS) by directly targeting angiotensin II Type 1 receptor (AT1R) mRNA, reducing its expression and attenuating angiotensin II (Ang II) signaling. In VSMCs, it promotes phenotypic switching and contributes to vascular remodeling through the soluble guanylate cyclase/cyclic guanosine monophosphate (sGC/cGMP) pathway. These coordinated actions foster a pro-inflammatory, vasoconstrictive state that underpins hypertension development. MiR-155 acts as a central molecular link between inflammation and vascular dysfunction in essential hypertension by modulating endothelial function, vascular inflammation, and smooth muscle cell behavior. Its modulation highlights miR-155 as a potential therapeutic target to restore endothelial homeostasis and limit vascular damage in hypertensive patients.