Abstract P027: Hypertensive Cardiorenal Damage Is Aggravated In Axenic Mice

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Hendrik Bartolomaeus ◽  
Ellen G Avery ◽  
Ulrike Löber ◽  
Theda U Bartolomaeus ◽  
Chia-Yu Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Gut Microbiota ◽  
Organ Damage ◽  
Kidney Damage ◽  
Marker Genes ◽  
Tubular Damage ◽  
Metagenomic Sequencing ◽  
Germ Free ◽  
End Organ Damage ◽  
Colonization Status

Introduction: The gut microbiota is suspected to play a role in hypertension and hypertensive end organ damage. In the present study, we used germ-free mice to demonstrate that microbial colonization modulates the response to a hypertensive stimulus. Methods: Four-week-old male germ-free C57BL6/J littermates were randomized to remain germ-free (GF) or to receive microbiota transfer from SPF donor mice to achieve full colonization status (COL). At 12 weeks, Angiotensin (Ang) II was infused s.c. for 14 days (1.44mg/kg/d, osmotic minipumps) and 1% NaCl added to the drinking water; sham-treated mice served as control. After 14 days of AngII we assessed inflammation and organ damage. Results: Fecal bacterial load in COL mice was similar to SPF donor mice (qPCR). Shotgun metagenomic sequencing of fecal samples revealed hypertension-induced alterations in microbiome composition confirming previous reports. Serum metabolome analysis ( Biocrates MxP Quant 500) confirmed the absence of microbiota-dependent metabolites in GF. Interestingly, microbiota-dependent metabolites relevant for cardiovascular risk (TMAO, indoxyl sulfate) were elevated in hypertensive COL mice compared to sham-treated. Hypertensive kidney damage was aggravated in GF mice. However, marker genes for tubular damage ( Lcn2 ), inflammation ( Ccl2 ), and fibrosis ( Col1a3 ) showed a stronger increase in GF mice (fold changes [fc] COL vs. GF: 7.5 vs 11.0, 1.2 vs 3.3, 1.3 vs 2.2, respectively). Albuminuria (fc 2 vs 25) and histology for kidney fibrosis (fc 1.1 vs 1.4) confirmed the aggravated kidney damage in GF mice. Similarly, we observed an aggravated cardiac damage in GF mice. Flow cytometry of splenic lymphocytes showed that the adaptive immune response to AngII + 1% NaCl, as evidenced by Th17 (fc 1.4 vs 2) and CD8+ central memory cells, was intensified in GF mice. In vitro , naïve T cells isolated from GF mice more readily polarized into Th17 (26 ± 5%) compared to T cells from SPF mice (19 ± 1%). Conclusion: The bacterial colonization status has potent effects on the phenotypic response to a hypertensive stimulus, evident to varying degrees in hearts and kidneys. The inflammatory response and the end organ damage in GF compared to COL mice demonstrates the importance of the gut microbiota in hypertension.

scholarly journals Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice

2008 ◽  
Vol 9 (1) ◽  
pp. 65 ◽  
Author(s):  
Tomas Hrncir ◽  
Renata Stepankova ◽  
Hana Kozakova ◽  
Tomas Hudcovic ◽  
Helena Tlaskalova-Hogenova
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Gut Microbiota ◽  
Germ Free

scholarly journals Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage

2021 ◽  
Author(s):  
Elllen G Avery ◽  
Hendrik Bartolomaeus ◽  
Ariana Rauch ◽  
Chia-Yu Chen ◽  
Gabriele N'diaye ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Th17 Cells ◽  
Suppressor Cells ◽  
Short Chain Fatty Acids ◽  
Organ Damage ◽  
Microbial Colonization ◽  
Cardiac Damage ◽  
The Impact ◽  
Colonization Status

Aims: Hypertension (HTN) can lead to heart and kidney damage. The gut microbiota has been linked to HTN, although it is difficult to estimate its significance due to the variety of other features known to influence HTN. Methods and Results: In the present study, we used germ-free (GF) and colonized (COL) littermate mice to quantify the impact of microbial colonization on organ damage in HTN. Four-week-old male GF C57BL/6J littermates were randomized to remain GF or receive microbial colonization. HTN was induced by subcutaneous infusion with angiotensin (Ang) II (1.44mg/kg/d) and 1% NaCl in the drinking water; sham-treated mice served as control. Renal damage was exacerbated in GF mice, whereas cardiac damage was more comparable between COL and GF, suggesting that the kidney is more sensitive to microbial influence. Multivariate analysis revealed a larger effect of HTN in GF mice. Serum metabolomics demonstrated that the colonization status influences circulating metabolites relevant to HTN. Importantly, GF mice were deficient in anti-inflammatory fecal short-chain fatty acids (SCFA). Flow cytometry showed that the microbiome has an impact on the induction of anti-hypertensive myeloid-derived suppressor cells and pro-inflammatory Th17 cells in HTN. In vitro inducibility of Th17 cells was significantly higher for cells isolated from GF than conventionally raised mice. Conclusion: Microbial colonization status of mice had potent effects on their phenotypic response to a hypertensive stimulus, and the kidney is a highly microbiota-susceptible target organ in HTN. The magnitude of the pathogenic response in GF mice underscores the role of the microbiome in mediating inflammation in HTN.

scholarly journals IL-2 Protects Lupus-Prone Mice from Multiple End-Organ Damage by Limiting CD4−CD8− IL-17–Producing T Cells

2014 ◽  
Vol 193 (5) ◽  
pp. 2168-2177 ◽  
Author(s):  
Masayuki Mizui ◽  
Tomohiro Koga ◽  
Linda A. Lieberman ◽  
Jessica Beltran ◽  
Nobuya Yoshida ◽  
...  
Keyword(s):  
T Cells ◽  
Organ Damage ◽  
End Organ Damage

Redefinition of Hypereosinophilic Disorders Based on an Analysis of 28 Cases of FIP1 L1-PDGFRA Negative Persistent Unexplained Eosinophilia (PUE) with Eosinophil End-Organ Damage (EEOD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3310-3310 ◽  
Author(s):  
Finella Brito-Babapulle ◽  
Nicholas C.P. Cross
Keyword(s):  
T Cells ◽  
Chronic Illness ◽  
Clinical Symptoms ◽  
Organ Damage ◽  
Therapeutic Trial ◽  
Female Ratio ◽  
End Organ Damage ◽  
Pdgfra Gene ◽  
Eosinophil Counts

Abstract In 1997 the term eosinophil end-organ damage(EEOD) was introduced to facilitate management of patients with high eosinophil counts in whom damage to organs such as heart, lungs, and skin by eosinophils was associated with persistent unexplained eosinophilia (no obvious cause for eosinophilia was identified). In 2003 Cools et al identified the presence of the FIP1L1-PDGFRA gene as the causation of eosinophilia in 50% of cases of hypereosinophilic syndromes with end organ damage. Cases which are negative for this gene and a Tcell clone appear to form a distinctive group whose aetiopathogenesis and clinical significance are different. In order to identify the extent of end organ damage in FIP1L1-PDGFRA negative cases and/or identify rarer causes of unexplained eosinophilia in all cases of eosinophilia presenting from 14.06.2002 to 14.06.2006, we looked at all patients who had persistent eosinophilia present on two separate blood tests done I month apart with eosinophil counts greater than 1–1.5 x 10 9/l. All cases of unexplained eosinophilia (Eosinophil count greater than 1– 1.5 x 10 9/L) seen at our institution in a 4 year period in whom no obvious cause of eosinophilia was found were evaluated for the presence of the FIP1L1-PDGFRA gene, TEL-PDGFRB and variant BCR-ABL gene. Of 40 cases seen 2 men were FIP1L1-PDGFRA positive, 3 others (2 men and 1 woman) had myeloproliferative diseases, I man had clozapine induced eosinophilia, one woman Kimura Weils disease and 1 man had cutaneous mastocytosis . There were 28 cases (14 women, 2 children,12 men) who were FIP1L1 -PDGFRA negative and had persistent unexplained eosinophilia without clonal T cells. These cases were followed up over a 4 year period and tested serially for damage to end organs by eosinophils. FIP1L1-PDGFRA was tested and found negative on two separate occasions. Ig E levels had to be less then 500 iu/l to exclude allergy and a therapeutic trial of mebendazole 100mg daily for three days was given in all cases even if parasite testing did not identify a parasitic infestation. There were 28 cases (14 women, 2 children,12 men) who were FIP1L1-PDGFRA negative which contrasts with the Male Female ratio seen in FIP1 L1-PDGFRA positive cases in which males predominate. The age ranged from 9–80. Four year follow up identified a chronic illness in these cases with no damage to vital organs. Clinical symptoms complained of included fatigue(28), joint and muscle pains(28), skin rashes(10), blackouts(1), thrombotic events(2), diarrhoea(2), fasciitis(2), gastroenteritis(2), cough(2), and breathlessness(2). No organomegaly was seen. In one clonal T cells were identified on serial testing after 1 year of follow up. We conclude that cases of FIP1L1-PDGFRA negative hypereosinophilia are a distinct group with a chronic illness mainly affecting skin and joints who respond well to symptomatic treatment, oral steroids, or hydroxyurea. We believe that hypereosinophilic diorders need to be redined as PUEand EEOD. When both PUE and EEOD are present the diagnosis is HES.

scholarly journals Immune mechanisms in arterial hypertension. Recent advances

2021 ◽  
Author(s):  
Ulrich O. Wenzel ◽  
Heimo Ehmke ◽  
Marlies Bode
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Organ Damage ◽  
T Cell Subsets ◽  
Blood Pressure Elevation ◽  
End Organ Damage ◽  
Pressure Elevation ◽  
Recent Advances

AbstractIncreasing evidence indicates that hypertension and hypertensive end-organ damage are not only mediated by hemodynamic injury. Inflammation also plays an important role in the pathophysiology and contributes to the deleterious consequences of this disease. Cells of the innate immune system including monocyte/macrophages and dendritic cells can promote blood pressure elevation via effects mostly on kidney and vascular function. Moreover, convincing evidence shows that T and B cells from the adaptive immune system are involved in hypertension and hypertensive end-organ damage. Skin monocyte/macrophages, regulatory T cells, natural killer T cells, and myeloid-derived suppressor cells have been shown to exert blood pressure controlling effects. Sodium intake is undoubtedly indispensable for normal body function but can be detrimental when taken in excess of dietary requirements. Sodium levels also modulate the function of monocyte/macrophages, dendritic cells, and different T cell subsets. Some of these effects are mediated by changes in the microbiome and metabolome that can be found after high salt intake. Modulation of the immune response can reduce severity of blood pressure elevation and hypertensive end-organ damage in several animal models. The purpose of this review is to briefly summarize recent advances in immunity and hypertension as well as hypertensive end-organ damage.

scholarly journals Loss of Salt Sensing Kinase, SGK1, in T cells abrogates Memory Cell Formation, Hypertension and End‐Organ Damage

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Hana A. Itani ◽  
Arvind Pandey ◽  
Allison E. Norlander ◽  
David G. Harrison
Keyword(s):  
T Cells ◽  
Cell Formation ◽  
Memory Cell ◽  
Organ Damage ◽  
End Organ Damage

Abstract 005: Loss of Interleukin 21 Protects Against Hypertension and Associated Inflammation and End Organ Damage

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Bethany L Dale ◽  
Arvind Pandey ◽  
Fanny Laroumanie ◽  
Hana Itani ◽  
Liang Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Angiotensin Ii ◽  
B Cell ◽  
Organ Damage ◽  
Ang Ii ◽  
End Organ Damage ◽  
Tfh Cells ◽  
Interleukin 21 ◽  
Endothelium Dependent Relaxation

T cell derived cytokines such as interferon gamma (IFNγ) and interleukin 17A (IL17A) are upregulated by and can promote angiotensin II-induced hypertension and end-organ damage. Interleukin 21 (IL21) is produced primarily by T follicular helper (Tfh) cells and has the potential to promote IL17A and IFNγ production from T effector cells while inhibiting T regulatory cells. IL21 is also a potent activator of germinal center (GC) B cells. Thus, we hypothesize that IL21 promotes hypertension and hypertensive end-organ damage through its effect on T cell polarization and GC B cell activation. The data indicate that indeed IL21 -/- mice exhibit a 30 mmHg reduction in blood pressure in response to 4 weeks of angiotensin II (Ang II) infusion compared to age-matched wild type (WT) mice (p=0.0275). IL21 mRNA expression increases 1.5 fold in splenic T cells in response to Ang II infusion (p=0.015). Moreover, Tfh cells and GC B cells are increased in the aortas of WT mice after Ang II infusion (p=0.0136 and p=0.0067, respectively). Further, IL17A production from splenic CD4+ T cells and IFNγ production from splenic CD8+ T cells was reduced in IL21 -/- mice compared to WT mice (p=0.0025 and p=0.0237, respectively) following Ang II infusion. Renal function was assessed by measuring albuminuria. WT mice developed 2-fold more albuminuria compared to IL21 -/- mice in response to Ang II infusion (p=0.0349). Lastly, Ang II infusion impaired endothelium-dependent relaxation to acetylcholine in mesenteric vessels from WT mice (52.9% vs 17.5%; p=<0.0001). IL21 -/- mice demonstrated moderately impaired endothelium-dependent relaxation at baseline (34.9%) but interestingly, there was no further impairment in these vessels following Ang II infusion. Taken together, these studies suggest that IL21 and the Tfh cell–GC B cell axis may play a key role in hypertension and hypertensive end-organ damage.

End Organ Damage in Hypertensive Geriatric Age Group: A Cross Sectional Study

2017 ◽  
Vol 1 (3) ◽  
pp. 10-16
Author(s):  
Prakashkumar Kyada ◽  
Kunal Jadhav ◽  
T. K. Biswas ◽  
Varshil Mehta ◽  
Sojib Bin Zaman
Keyword(s):  
Ventricular Hypertrophy ◽  
Organ Damage ◽  
Cross Sectional Study ◽  
Left Ventricular ◽  
Age Group ◽  
Sectional Study ◽  
Isolated Systolic Hypertension ◽  
Cross Sectional ◽  
End Organ Damage ◽  
Common Risk Factors

Objective: Hypertension is one of the common risk factors for cardiovascular and cerebrovascular diseases/disorders A developing country like India faces the double burden of communicable and non-communicable diseases; of the which, hypertension is the most important treatable cause of mortality and morbidity with loss of functional capacity and decline in the quality of life. Aim: To study the prevalence of end organ damage in the hypertensive geriatric age group. Method: The present study was a cross sectional study, conducted in 150 elderly patients admitted in MGM Hospital, Navi Mumbai, India with the diagnosis of stage I or II hypertension from 2011 to 2013. Results: Data analysis of the present study showed that 68% of elderly population aged between 60 to 69 years were suffering from hypertension. Compared to males, females had a higher rate of target organ damage. This study found that out of all patients with total end organ damage, 54.6 % had CVS complications, 15.7 % had hypertensive retinopathy, 25.9 % and 18.51 had raised creatinine and proteinuria respectively. 19.4 % had cerebrovascular accident (CVA) complications. Among Cardiovascular related complications Coronary artery disease (CAD) was found in 21 patients, out of them 7 had Congestive cardiac Failure (CCF). Left Ventricular Hypertrophy (LVH) was the most common complication and seen in 38 patients. 13.8 % patients had Regional Wall Motion Abnormality (RWMA) Conclusion: The present study concluded that Isolated Systolic Hypertension (ISH) is the commonest type of hypertension in geriatric age group. This study concluded that the most common risk factors of HTN in the elderly are sedentary life style, dyslipidemia and extra salt intake while the most common end organ damage was observed to be Left Ventricular Hypertrophy followed by renal dysfunction. Keywords:  Hypertension,  Isolated Systolic Hypertension, Dyslipidemia.

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