Human monocyte transcriptional profiling identifies IL‐18 receptor accessory protein and lactoferrin as novel immune targets in hypertension

Alexander, Matthew; Norlander, Allison E.; Elijovich, Fernando; Atreya, Ravi V.; Gaye, Amadou Thierno; Gnecco, Juan; Laffer, Cheryl L.; Galindo, Cristi L.; Madhur, Meena S

doi:10.1111/bph.14364

Cited by 22 publications

(15 citation statements)

References 53 publications

(73 reference statements)

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“…Previously, several studies identified genes which might be potentially associated with different features of the metabolic profile [ 7 , 8 , 9 ]. Additionally, previous studies suggested that selected polymorphisms in LTF , LRP1 , and LRP2 genes might be associated with the prevalence of metabolic abnormalities [ 7 , 11 , 12 , 23 , 24 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…This gene is highly polymorphic with the presence of several common alleles in the general population [ 27 , 28 ]. Previously, several studies have suggested that some SNPs in LTF gene might be associated with the prevalence of metabolic abnormalities [ 11 , 12 , 23 ]; however, none of the studies evaluated the association between LTF, LRP1 and LRP2 genes polymorphisms with the prevalence of metabolically healthy or metabolically unhealthy obesity. Similarly to our results, Marcil et al [ 12 ] in a study conducted on 1749 French Canadians aged 9, 13 and 16 years and found a significant difference in allele frequencies between subjects with and without metabolic syndrome for the LTF rs2239692 polymorphism.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the association between LTF gene polymorphisms and blood pressure was reported, with Alexander et al [ 23 ] observing that LTF rs1126478 was over-represented in subjects with hypertension compared to controls. Using a recessive genetic model, researchers found that the frequency of homozygosity for the minor allele (GG) in hypertensive group significantly increased relative to controls.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic Health in Obese Subjects—Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?

et al. 2020

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This study aimed to evaluate the association of genetic variants in lactoferrin (LTF) metabolism-related genes with the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). In total, 161 MHO and 291 MUHO subjects were recruited to the study. The following polymorphisms were genotyped: low-density lipoprotein receptor-related protein (LRP) 2 rs2544390, LRP1 rs4759277, LRP1 rs1799986, LTF rs1126477, LTF rs2239692 and LTF rs1126478. We found significant differences in the genotype frequencies of LTF rs2239692 between MHO and MUHO subjects, with the CT variant associated with lower odds of developing metabolic syndrome than the TT variant. In the total population, significant differences in body weight and waist circumference (WC) were identified between LTF rs1126477 gene variants. A similar association with WC was observed in MUHO subjects, while significant differences in body mass index and low-density lipoprotein cholesterol levels were discovered between LTF rs1126477 gene variants in MHO subjects. Besides, there were significant differences in diastolic blood pressure between LRP1 rs1799986 gene variants in MUHO subjects, as well as in WC and high-density lipoprotein cholesterol levels between LRP1 rs4759277 gene variants in MHO subjects. In conclusion, selected lactoferrin and lactoferrin receptor-related gene variants may be associated with the prevalence of metabolically healthy or metabolically unhealthy obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolic Health in Obese Subjects—Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?

et al. 2020

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“…Alexander et al confirmed that monocytes showed enhanced pro-inflammatory gene expression in adult subjects with hypertension and identified IL18 receptor accessory protein as a potential novel mediator of arterial hypertension. 59…”

Section: Discussionmentioning

confidence: 99%

Angiotensinogen and interleukin 18 in serum and urine of children with kidney cysts

Plesiński¹,

Adamczyk

Świętochowska

et al. 2019

J Renin Angiotensin Aldosterone Syst

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Background: The most common disease associated with the presence of kidney cysts in the population is autosomal dominant polycystic kidney disease (ADPKD), which finally leads to end-stage renal disease. Method: The study evaluated serum and urinary concentration of angiotensinogen (AGT) and interleukin 18 (IL-18) in a group of 39 children with renal cysts of different aetiology. Results: Serum and urinary AGT concentration in children with renal cysts was higher compared to controls, regardless of the underlying background and gender. Serum IL-18 concentration was lower, in contrast, and the concentration of IL-18 in the urine did not differ between affected and healthy children. Negative correlation between urinary IL-18 concentration and systolic and mean arterial blood pressure was noted. Conclusions: Higher AGT levels in serum and urine in children with renal cysts may indicate the activation of the renin–angiotensin–aldosterone system, including its intrarenal part, even before the onset of hypertension. Lower serum concentration of IL-18 in children with kidney cysts may indicate the loss of the protective role of this cytokine with the occurrence of hypertension.

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“…Similarly, monocytes obtained from hypertensive patients demonstrate exaggerated production of IL-1β when isolated and stimulated in vitro with known hypertensive stimuli like angiotensin II [ 127 ]. Importantly, a recent unbiased next-generation RNA sequencing approach revealed the differential expression of 60 genes between monocytes isolated from normotensive and hypertensive individuals [ 128 ]. Most of those genes were involved in the IL-1β pathway [ 128 ], thus implying an overstimulation of the inflammasome pathway in these cells during hypertension.…”

Section: Novel Roles Of the Nlrp3 Inflammasome And Pyroptosis In Bmentioning

confidence: 99%

Emerging Role of the Inflammasome and Pyroptosis in Hypertension

Miguel

Pelegrı́n

Baroja‐Mazo

et al. 2021

IJMS

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Inflammasomes are components of the innate immune response that have recently emerged as crucial controllers of tissue homeostasis. In particular, the nucleotide-binding domain, leucine-rich-containing (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex platform involved in the activation of caspase-1 and the maturation of interleukin (IL)-1β and IL-18, which are mainly released via pyroptosis. Pyroptosis is a caspase-1-dependent type of cell death that is mediated by the cleavage of gasdermin D and the subsequent formation of structurally stable pores in the cell membrane. Through these pores formed by gasdermin proteins cytosolic contents are released into the extracellular space and act as damage-associated molecular patterns, which are pro-inflammatory signals. Inflammation is a main contributor to the development of hypertension and it also is known to stimulate fibrosis and end-organ damage. Patients with essential hypertension and animal models of hypertension exhibit elevated levels of circulating IL-1β. Downregulation of the expression of key components of the NLRP3 inflammasome delays the development of hypertension and pharmacological inhibition of this inflammasome leads to reduced blood pressure in animal models and humans. Although the relationship between pyroptosis and hypertension is not well established yet, pyroptosis has been associated with renal and cardiovascular diseases, instances where high blood pressure is a critical risk factor. In this review, we summarize the recent literature addressing the role of pyroptosis and the inflammasome in the development of hypertension and discuss the potential use of approaches targeting this pathway as future anti-hypertensive strategies.

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Human monocyte transcriptional profiling identifies IL‐18 receptor accessory protein and lactoferrin as novel immune targets in hypertension

Abstract: These data demonstrate that monocytes exhibit enhanced pro-inflammatory gene expression in hypertensive individuals and identify IL18RAP and LTF as potential novel mediators of human hypertension.

Cited by 22 publications

References 53 publications

Metabolic Health in Obese Subjects—Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?

Metabolic Health in Obese Subjects—Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?

Angiotensinogen and interleukin 18 in serum and urine of children with kidney cysts

Emerging Role of the Inflammasome and Pyroptosis in Hypertension

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