scholarly journals POS0418 SPLENIC EXTRAMEDULLARY HEMATOPOIESIS IS OMNIPRESENT AND CORRELATES WITH DISEASE SEVERITY IN THE LUPUS NZB/W F1 MURINE MODEL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 438.1-438
Author(s):  
S. Doumas ◽  
M. Grigoriou ◽  
A. Banos ◽  
C. Giakopoulou ◽  
I. Mitroulis ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Murine Model ◽  
Target Organ Damage ◽  
Cell Activity ◽  
Organ Damage ◽  
Extramedullary Hematopoiesis ◽  
Target Organ ◽  
Massive Splenomegaly ◽  
Hematopoietic Stem

Background:Extramedullary hematopoiesis (EMH) is increasingly recognized as an integral component of systemic inflammatory diseases; compared to their bone marrow counterparts, hematopoietic progenitors of EMH have an enhanced role in target organ damage1,2. We have found that β-glucan -a non-specific inducer of reprograming of innate immunity- results in dramatic EMH with marked increase in Long-Term (LT)-HSCs, massive splenomegaly and worsening of nephritis in the NZB/W F1 lupus murine model (unpublished data).Objectives:To investigate EMH’s time course and contribution to inflammatory target-organ damage (kidney) in the NZB/W F1 lupus murine model.Methods:Spleens and kidneys were isolated from female NZB/W F1, at pre-nephritic stage (3-month-old) and nephritic stage (>6-month-old), and age/sex matched C57BL/6 (WT controls). Single-cell suspensions of spleens were analyzed by flow cytometry for Hematopoietic Stem and progenitor cells (HSPCs) phenotyping. Formalin-fixed and paraffin-embedded sections of spleens and kidneys were stained with conventional histological stains (H&E, Silver, Trichrome Masson). Spleens were histologically assessed for the presence of ΕΜΗ and kidneys were assessed for activity and chronicity through the NIH Lupus nephritis scoring system.Results:Histological analysis revealed that NZW/B F1 mice at the nephritic stage display massive splenomegaly with concomitant expansion of the red pulp, increased presence of megakaryocytes and disorganized splenic architecture. This is further corroborated by the flow cytometry analysis which demonstrated a significant increase of all HSPCs subsets (Long-term/Short-term Hematopoietic Stem Cells and Multipotent progenitors) compared to the C57BL/6 WT controls at nephritic stage. The degree of HSPC expansion and splenic architecture disorganization correlates strongly with the activity of lupus nephritis as quantified by the NIH scoring system. Of note, evidence of splenic EMH were present even in 3-month-old animals before overt nephritis ensues.Conclusion:Extramedullary hematopoiesis is present before overt nephritis and is dramatically expanded at the nephritic stage of the NZW/B F1 mouse model. The degree of EMH positively correlates with the severity of lupus nephritis. These data support a pathogenic role of EMH, and spleen derived HSPCs, in driving lupus nephritis.References:[1]Regan-Komito, D., Swann, J.W., Demetriou, P., Cohen, E.S., Horwood, N.J., Sansom, S.N., Griseri, T., 2020. GM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis. Nature Communications 11, 155.[2]Griseri, T., McKenzie, B.S., Schiering, C., Powrie, F., 2012. Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation. Immunity 37, 1116–1129.Acknowledgements:This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742390)Disclosure of Interests:None declared

Short-term ACE inhibition confers long-term protection against target organ damage

2012 ◽  
Vol 35 (6) ◽  
pp. 604-610 ◽  
Author(s):  
Taben M Hale ◽  
Susan J Robertson ◽  
Kevin D Burns ◽  
Denis deBlois
Keyword(s):  
Target Organ Damage ◽  
Ace Inhibition ◽  
Organ Damage ◽  
Target Organ ◽  
Short Term

scholarly journals Comparative efficacy of nifedipine-retard and atenolol in correction of target organ damage in patients with essential hypertension

2006 ◽  
Vol 12 (3) ◽  
pp. 194-199
Author(s):  
I. V. Emelyanov ◽  
S. V. Villevalde ◽  
E. A. Lyasnikova ◽  
O. M. Moiseeva
Keyword(s):  
Essential Hypertension ◽  
Blood Pressure Monitoring ◽  
Target Organ Damage ◽  
Randomized Study ◽  
Hypotensive Effect ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Term Therapy

The aim of the study was to assess the relationship between antihypertensive effect of nifedipine-retard and atenolol long-term therapy and changes of target organ damage (heart, carotid arteries, endothelial function) in patients with essential hypertension (HT) 2 stage. 45 patients with AH were included in the open prospective randomized study: 24 received nifedipine-retard 40 mg per day, 21 received atenolol 50 - 100 mg per day. There were no clinical and haemodynamic discrepanses between the groups at basline. Ambulatory blood pressure monitoring (ABPM), echocardiography (EchoCG), assess of endothelium-dependent and endothelium-independent vasodilatation were performed at basal state (after 14 days wash-out period) and after 6-month therapy. Both nifedipine-retard and atenolol had comparable and apparent hypotensive effect. The regression of left ventricular hypertrophy and the improvement of left ventricle diastolic function became evident during nifedipine-retard therapy in contrast to atenolol treatment. Long-term nifedipine-retard therapy is accompanied by an increase of volume flow velocity in arteria radialis and leads to correction of endothelium dysfunction in patients with HT.

scholarly journals Target Organ Damage and the Long Term Effect of Nonadherence to Clinical Practice Guidelines in Patients with Hypertension: A Retrospective Cohort Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Tadesse Melaku Abegaz ◽  
Yonas Getaye Tefera ◽  
Tamrat Befekadu Abebe
Keyword(s):  
Cohort Study ◽  
Clinical Practice ◽  
Practice Guidelines ◽  
Retrospective Cohort ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Term Effect ◽  
Long Term Effect

Background. There was limited published data on target organ damage (TOD) and the effect of nonadherence to practice guidelines in Ethiopia. This study determined TOD and the long term effect of nonadherence to clinical guidelines on hypertensive patients. Methods. An open level retrospective cohort study has been employed at cardiac clinic of Gondar university hospital for a mean follow-up period of 78 months. Multivariate Cox regression was conducted to test associating factors of TOD. Results. Of the total number of 612 patients examined, the overall prevalence of hypertensive TOD was 40.3%. The presence of comorbidities, COR = 1.073 [1.01–1.437], AOR = 1.196 [1.174–1.637], and nonadherence to clinical practice guidelines, COR = 1.537 [1.167–2.024], AOR = 1.636 [1.189–2.251], were found to be predicting factors for TOD. According to Kaplan-Meier analysis patients who were initiated on appropriate medication tended to develop TOD very late: Log Rank [11.975 (p=0.01)]. Conclusion. More than forty percent of patients acquired TOD which is more significant. Presence of comorbidities and nonadherence to practice guidelines were correlated with the incidence of TOD. Appropriate management of hypertension and modification of triggering factors are essential to prevent complications.

scholarly journals Causes and consequences of sympathetic overactivity in hypertension

2003 ◽  
Vol 9 (3) ◽  
pp. 81-88 ◽  
Author(s):  
E. V. Shlyakhto ◽  
A. Ο. Conrady
Keyword(s):  
Metabolic Disorders ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Blood Pressure Elevation ◽  
Sympathetic Overactivity ◽  
Long Term Prognosis ◽  
The Impact

The paper is dedicated to methods to assess sympathetic activity in humans and role of simpathetic nervous system in development and progression of arterial hypertension. The impact of simpathetic overactivity into blood pressure elevation is discussed as consequences of sympathetic overactivity from target organ damage, metabolic disorders and long-term prognosis.

scholarly journals Weight-Loss Strategies for Prevention and Treatment of Hypertension: A Scientific Statement From the American Heart Association

Hypertension ◽  
2021 ◽  
Author(s):  
Michael E. Hall ◽  
Jordana B. Cohen ◽  
Jamy D. Ard ◽  
Brent M. Egan ◽  
John E. Hall ◽  
...  
Keyword(s):  
Weight Loss ◽  
Lifestyle Modification ◽  
Kidney Diseases ◽  
Target Organ Damage ◽  
Heart Association ◽  
Organ Damage ◽  
The United States ◽  
Target Organ ◽  
Renal Diseases

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

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