arterial hypertension
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2022 ◽  
Vol 40 (1) ◽  
pp. 1-12
Sudarshan Rajagopal ◽  
Yen-Rei A. Yu

2022 ◽  
Vol 40 (1) ◽  
pp. 13-27
Alexander E. Sherman ◽  
Rajan Saggar ◽  
Richard N. Channick

2022 ◽  
Vol 17 (1) ◽  
Zhijie Yu ◽  
Jun Xiao ◽  
Xiao Chen ◽  
Yi Ruan ◽  
Yang Chen ◽  

AbstractPulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH. Graphical Abstract

О.А. Осипова ◽  
Е.В. Гостева ◽  
О.Н. Белоусова ◽  
Н.И. Жернакова ◽  
Н.И. Клюшников ◽  

В статье рассмотрены вопросы развития фиброза и иммунного воспаления у больных артериальной гипертензией (АГ) с острым ишемическим инсультом (ИИ) в пожилом возрасте. Цель исследования - изучение возраст-ассоциированных особенностей концентрации маркеров фиброза (металлопротеиназы-9, тканевого ингибитора матриксных металлопротеиназ-1, их соотношения ММП-9/ТИМП-1), иммунного воспаления (TNF-α, IL-1β, INF-γ) у больных АГ с ИИ. В исследование были включены 86 больных АГ II степени, из которых 42 человека - среднего возраста (53±5 лет) и 44 - пожилого (66±5 лет), контрольную группу составили 22 пациента пожилого возраста с АГ без ИИ в анамнезе. Критерии включения - пациенты с АГ, поступившие в стационар в остром периоде первого церебрального инсульта. Установлено, что у пожилых больных АГ с ИИ показатели инфламэйджинга и маркеры фиброза были достоверно выше, чем у лиц среднего возраста. Уровень IL-1β был выше на 31,7 % (р<0,01), TNF-α - на 55,7 % (р<0,001), INF-γ - на 36,6 % (р<0,01), уровень ММП-9 - на 46,4 % (р<0,01), ТИМП-1 - на 21,2 % (р<0,01), ММП-9/ТИМП-1 - на 19,6 % (р<0,01) в пожилом возрасте по сравнению с больными среднего возраста с АГ и острым ИИ. Таким образом, установлено, что больные АГ с ИИ имеют нарушения процессов инфламейджинга, синтеза и деградации внеклеточного матрикса, особенно выраженные в пожилом возрасте. The article deals with the development of fibrosis and immune inflammation in patients with arterial hypertension and acute ischemic stroke in old age. The aim of the study was to study age-associated features of the concentration of fibrosis markers (metalloproteinase-9, tissue inhibitor of matrix metalloproteinases-1, their ratio MMP-9/TIMP-1), immune inflammation (TNF-α, IL-1β, INF-γ) in patients with arterial hypertension and ischemic stroke (AI). The study included 86 patients with arterial hypertension (AH) of the 2nd degree, of which 42 were middle-aged (53±5 years) and 44 elderly (66±5 years). The control group consisted of 22 elderly patients with AH without a history of AI. The criteria for inclusion in the study are patients with hypertension who were admitted to the hospital in the acute period of the first cerebral stroke. It was found that in elderly patients with hypertension with AI, the indicators of inflamaging and fibrosis markers were significantly higher than in middle-aged people. The level of IL-1β was 31,7 % higher (p<0,01), TNF-α by 55,7 % (p<0,001), INF-γ by 36,6 % (p<0,01), the level of MMP-9 was 46,4 % higher (p<0,01), TIMP-1 by 21,2 % (p<0,01), MMP-9/TIMP-1 by 19,6 % (p<0,01) in the elderly compared to middle-aged patients with hypertension and acute AI. Thus, it was found that patients with arterial hypertension and ischemic stroke have violations of the processes of inflamaging, synthesis and degradation of the extracellular matrix, especially pronounced in old age.

2022 ◽  
Alexey N. Sumin ◽  
Nina S. Gomozova ◽  
Anna V. Shcheglova ◽  
Oleg G. Arkhipov

Abstract Objective of this study was to compare right ventricular echocardiography parameters in urbanized hypertensive patients of the Shor and non-indigenous ethnic groups in the Mountain Shoria region. Methods The study included patients with arterial hypertension: 58 Shors and 50 non-indigenous urbanized residents, comparable in age, and divided by ethnicity and gender into 4 groups: Shors men (n = 20), Shors women (n = 38), non-indigenous men (n = 15) and non-indigenous women (n = 35). All underwent echocardiographic examination, and the right heart parameters were studied. Results Shor men with arterial hypertension had the lowest values ​​of the pulmonary artery index, the right atrium dimensions, and the highest values ​​of the blood flow velocity in the right ventricle, et' and st' in comparison with non-indigenous men. Shor women have the lowest values Et and Et/At ratios. RV diastolic dysfunction was detected mainly in women, somewhat more often in Shors. Ethnicity was one of the factors associated with the right ventricular diastolic dysfunction presence. Among the factors associated with the RV diastolic dysfunction were risk factors (smoking, obesity), blood pressure, gender, ethnicity, and left ventricular parameters (diastolic dysfunction and the myocardial mass increase). Conclusion Our study established the influence of ethnic differences on the right heart echocardiographic parameters in Shors and Caucasians with arterial hypertension. The revealed differences should improve the assessment of the right heart structure and function in patients with arterial hypertension from small ethnic groups, which will help to improve the diagnosis and treatment of such patients.

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 170
Linh Ho ◽  
Nazir Hossen ◽  
Trieu Nguyen ◽  
Au Vo ◽  
Fakhrul Ahsan

Pulmonary arterial hypertension (PAH) is a disease that progress over time and is defined as an increase in pulmonary arterial pressure and pulmonary vascular resistance that frequently leads to right-ventricular (RV) failure and death. Epigenetic modifications comprising DNA methylation, histone remodeling, and noncoding RNAs (ncRNAs) have been established to govern chromatin structure and transcriptional responses in various cell types during disease development. However, dysregulation of these epigenetic mechanisms has not yet been explored in detail in the pathology of pulmonary arterial hypertension and its progression with vascular remodeling and right-heart failure (RHF). Targeting epigenetic regulators including histone methylation, acetylation, or miRNAs offers many possible candidates for drug discovery and will no doubt be a tempting area to explore for PAH therapies. This review focuses on studies in epigenetic mechanisms including the writers, the readers, and the erasers of epigenetic marks and targeting epigenetic regulators or modifiers for treatment of PAH and its complications described as RHF. Data analyses from experimental cell models and animal induced PAH models have demonstrated that significant changes in the expression levels of multiple epigenetics modifiers such as HDMs, HDACs, sirtuins (Sirt1 and Sirt3), and BRD4 correlate strongly with proliferation, apoptosis, inflammation, and fibrosis linked to the pathological vascular remodeling during PAH development. The reversible characteristics of protein methylation and acetylation can be applied for exploring small-molecule modulators such as valproic acid (HDAC inhibitor) or resveratrol (Sirt1 activator) in different preclinical models for treatment of diseases including PAH and RHF. This review also presents to the readers the application of microfluidic devices to study sex differences in PAH pathophysiology, as well as for epigenetic analysis.

2022 ◽  
Vol 8 ◽  
Anna Foley ◽  
Benjamin E. Steinberg ◽  
Neil M. Goldenberg

Inflammasomes are multi-protein complexes that sense both infectious and sterile inflammatory stimuli, launching a cascade of responses to propagate danger signaling throughout an affected tissue. Recent studies have implicated inflammasome activation in a variety of pulmonary diseases, including pulmonary arterial hypertension (PAH). Indeed, the end-products of inflammasome activation, including interleukin (IL)-1β, IL-18, and lytic cell death (“pyroptosis”) are all key biomarkers of PAH, and are potentially therapeutic targets for human disease. This review summarizes current knowledge of inflammasome activation in immune and vascular cells of the lung, with a focus on the role of these pathways in the pathogenesis of PAH. Special emphasis is placed on areas of potential drug development focused on inhibition of inflammasomes and their downstream effectors.

2022 ◽  
pp. 00549-2021
Krit Dwivedi ◽  
Robin Condliffe ◽  
Michael Sharkey ◽  
Robert Lewis ◽  
Samer Alabed ◽  

BackgroundPatients with pulmonary hypertension (PH) and lung disease may pose a diagnostic dilemma between idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-CLD). The prognostic impact of common CT parenchymal features is unknown.Methods660 IPAH and PH-CLD patients assessed between 2001–19 were included. Reports for all CT scans one year prior to diagnosis were analysed for common lung parenchymal patterns. Cox regression and Kaplan-Meier analysis was performed.ResultsAt univariate analysis of the whole cohort, centrilobular ground glass (CGG) changes (Hazard Ratio, HR 0.29) and ground glass opacification (GGO, HR 0.53) predicted improved survival while honeycombing (HR 2.79), emphysema (HR 2.09) and fibrosis (HR 2.38) predicted worse survival (p all <0.001). Fibrosis was an independent predictor after adjusting for baseline demographics, PH severity and DLco (HR 1.37, p<0.05). Patients with a clinical diagnosis of IPAH who had an absence of reported parenchymal lung disease (IPAH-noLD) demonstrated superior survival to patients diagnosed with either IPAH who had coexistent CT lung disease or PH-CLD (2-year survival of 85%, 60% and 46% respectively, p<0.05). CGG changes were present in 23.3% of IPAH-noLD and 5.8% of PH-CLD patients. There was no significant difference in survival between IPAH-noLD patients with or without CGG changes. PH-CLD patients with fibrosis had worse survival than those with emphysema.InterpretationRoutine clinical reports of CT lung parenchymal disease identify groups of patients IPAH and CLD-PH with significantly different prognoses. Isolated CGG changes are not uncommon in IPAH but are not associated with worse survival.

2022 ◽  
Jason Hong ◽  
Brenda Wong ◽  
Caroline Huynh ◽  
Brian Tang ◽  
Soban Umar ◽  

Rationale: The identification and role of endothelial progenitor cells (EPCs) in pulmonary arterial hypertension (PAH) remains controversial. Single-cell omics analysis can shed light on EPCs and their potential contribution to PAH pathobiology. Objectives: We aim to identify EPCs in rat lungs and assess their relevance to preclinical and human PAH. Methods: Differential expression, gene set enrichment, cell-cell communication, and trajectory reconstruction analyses were performed on lung endothelial cells from single-cell RNA-seq of Sugen-hypoxia, monocrotaline, and control rats. Relevance to human PAH was assessed in multiple independent blood and lung transcriptomic datasets. Measurements and Main Results: A subpopulation of endothelial cells (EA2) marked by Tm4sf1, a gene strongly implicated in cancer, harbored a distinct transcriptomic signature including Bmpr2 downregulation that was enriched for pathways such as inflammation and angiogenesis. Cell-to-cell communication networks specific to EA2 were activated in PAH such as CXCL12 signaling. Trajectory analysis demonstrated EA2 has a stem/progenitor cell phenotype. Analysis of independent datasets revealed Tm4sf1 is a marker for hematopoietic stem cells and is upregulated in PAH peripheral blood, particularly in patients with worse WHO functional class. EA2 signature genes including Procr and Sulf1 were found to be differentially regulated in the lungs of PAH patients and in PAH models in vitro, such as BMPR2 knockdown. Conclusions: Our study uncovered a novel Tm4sf1-marked stem/progenitor subpopulation of rat lung endothelial cells and demonstrated its relevance to preclinical and human PAH. Future experimental studies are warranted to further elucidate the pathogenic role and therapeutic potential of targeting EA2 and Tm4sf1 in PAH.

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