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Furthermore, markedly upregulated anti-inflammatory M2 macrophages reduced proinflammatory M1 macrophages, and CD8+ T cells were detected in stenotic kidneys treated with Lean-EVs compared with MetS-EVs, and renal vein levels of interleukin-1β were reduced. In vitro, coculture of Lean-EVs with activated T cells led to greater TGF-β-dependent regulatory T cells induction than did MetS-EVs. Therefore, the beneficial effects of mesenchymal stem cells-derived EVs on injured kidneys might be partly mediated by their content of TGF-β signaling components, which permitting increased Treg preponderance. Modulating EV cargo and transforming their functionality might be useful for renal repair.Orthostatic hypertension, which appears to be mediated through excess neurohumoral activation while standing, is a common blood pressure trait among patients with and without arterial hypertension. However, lack of consensus regarding the definition of orthostatic hypertension makes it difficult to assess the true prevalence of this condition. Orthostatic hypertension appears to predict the risk for progression to arterial hypertension in younger and risk of cardiovascular morbidity and mortality in older persons. Yet, the risk may differ between populations. Whether orthostatic hypertension indicates a generally increased risk of death, constitutes an intermediate variable in the causal pathway of cardiovascular risk factors, a simple measure of disease severity, or an independently acting mechanism is not known. Since both orthostatic hypotension and orthostatic hypertension herald increased risk of cardiovascular disease, it appears reasonable to screen the patients for abnormal orthostatic blood pressure responses using simple orthostatic testing. However, how presence of orthostatic hypertension may affect clinical management decisions such as the choice of antihypertensive drugs is currently difficult to ascertain. Clearly, this issue deserves more attention.Lowering blood pressure (BP) can lead to an initial decline in estimated glomerular filtration rate (eGFR). However, there is debate how much eGFR decline is acceptable. We performed a post hoc analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) and SPRINT (Systolic Blood Pressure Intervention Trial), which randomized patients to intensive or standard systolic BP-targets. We determined the relation between initial decline in mean arterial pressure and eGFR. Subsequently, we stratified patients to BP-target and initial eGFR decrease and assessed the relation with annual eGFR decline after 1 year. A total of 13 266 patients with 41 126 eGFR measurements were analyzed. Up to 10 mm Hg of BP-lowering, eGFR did not change. Hereafter, there was a linear decrease of 3.4% eGFR (95% CI, 2.9%-3.9%) per 10 mm Hg mean arterial pressure decrease. The observed eGFR decline based on 95% of the subjects varied from 26% after 0 mm Hg to 46% with a 40 mm Hg mean arterial pressure decrease. There was no difference in eGFR slope (P=0.37) according to initial eGFR decline and BP-target, with a decrease of 1.24 (95% CI, 1.09-1.39), 1.20 (95% CI, 0.97-1.43), and 1.14 (95% CI, 0.77-1.50) in the 5%, 5% to 20%, and >20% stratum during intensive and 0.95 (95% CI, 0.81-1.09), 1.23 (95% CI, 0.97-1.49), and 1.17 (95% CI, 0.65-1.69) mL/minute per 1.73 m2 per year during standard treatment. In patients at high cardiovascular risk with and without diabetes mellitus, we found no association between initial eGFR and annual eGFR decline during BP-lowering treatment. Our results support that an eGFR decrease up to 20% after BP lowering can be accepted and suggest that the limit can be extended up to 46% depending on the achieved BP reduction. Registration- URL https//www.clinicaltrials.gov; Unique identifier NCT00000620, NCT01206062.KL (klotho) levels decline with age, which is an important mechanistic driver of aging. KL gene deficiency is associated with hypertension. The purpose of this study is to investigate the potential role of H3K27me3 (histone 3 lysine [K] 27 trimethylation) in the regulation of KL gene expression and examine the related molecular pathways that may drive kidney cell aging. read more Kidneys were collected from 6-month-old WT (wild type; young WT), 30-month-old WT (aged WT), and 6- (young) and 20-month-old (aged) KL mutant mice, respectively. We demonstrated that the H3K27me3 level was increased in kidneys of aged WT and KL mutant mice versus young WT mice. Elevation of H3K27me3 levels was likely due to downregulation of the H3K27 (histone H3 Lys 27)-specific demethylase JMJD3 (the Jumonji domain containing-3) in the aged kidneys. Inhibition of PRC2 (polycomb repressive complex C2; histone trimethyltransferase) decreased the H3K27me3 levels leading to an increase in the expression of KL in cultured primary renal tubule cells assessed by Western blot and KL promoter activity assays. The chromatin immunoprecipitation qPCR assay revealed that H3K27me3 was physically associated with the KL promoter region. Furthermore, aging impaired the SGK1 (serum- and glucocorticoid-induced protein kinase 1)/FOXO3a (the forkhead box class O 3a) signaling leading to upregulation of p53 and p16 (aging markers) in the kidney of aged WT mice. KL may regulate the SGK1/FOXO3 signaling, which was decreased due to KL deficiency. Thus, aging-associated downregulation of KL gene expression may be partly attributed to upregulation of H3K27me3 levels. Downregulation of KL may impair the SGK1/FOXO3 signaling contributing to kidney cell aging.Hypertension is a condition with increased risk for subsequent adverse events, and treatment of hypertension is prescribed for primary prevention of adverse events. Primordial prevention is a concept that precedes primary prevention and focuses on risk factor prevention. Primordial prevention of hypertension consists of strategies to maintain blood pressure in a normal range and prevent development of elevated blood pressure or hypertension. Childhood is a period in which primordial prevention could be effective and if sustained throughout childhood could contribute to a healthier young adulthood. Targets for primordial prevention in childhood include preventing and reducing childhood obesity, achieving an optimal diet that includes avoiding excessive salt consumption, and removing barriers to physical activity and healthy sleep throughout childhood. Primordial prevention also includes the prenatal period wherein some maternal conditions and exposures are associated with higher blood pressure in child offspring.