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CD115, the receptor for colony stimulating factor 1, is essential for survival and differentiation of monocytes and macrophages and is therefore frequently used to define monocyte subsets and their progenitors in immunological assays. However, CD115 surface expression and detection by flow cytometry is greatly influenced by cell isolation and processing methods, organ source, and disease context. In a systematic analysis of murine monocytes, we define experimental conditions that preserve or limit CD115 surface expression and staining by flow cytometry. We also find that, independent of conditions, CD115 surface levels are consistently lower in Ly6Clo monocytes than in Ly6Chi monocytes, with the exception of Ly6Clo monocytes in the bone marrow. Furthermore, in contrast to IL-34, the presence of colony stimulating factor 1 impairs CD115 antibody staining in a dose-dependent manner, which, in a model of ischemic kidney injury with elevated levels of colony stimulating factor 1, influenced quantification of kidney monocytes. Thus, staining and experimental conditions affect quantitative and qualitative analysis of monocytes and may influence experimental conclusions. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA), characterised by low-renin hypertension, confers a high cardiovascular risk and is the most common cause of secondary hypertension, with an increased prevalence in patients with treatment-resistant hypertension. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice. Inhibitors of the renin-angiotensin system cause an increase in renin levels in patients with intact aldosterone regulation, and inadequate low renin with concurrent RAS inhibition (RASi) may therefore indicate PA, which could serve as a first look screening test for selection for formal work-up. We analysed patients between 2016–2018 with treatment-resistant hypertension who had inadequate low renin in the presence of RASi (i. e. at risk for PA) and who were offered systematic work-up with adrenal vein sampling (AVS). A total of 26 pts were included in the study (age 54.8 ± 11, male 65%). Mean office blood pressure (BP) was 154/95 mmHg on 4.5 antihypertensive drug classes. AVS had a high technical success rate (96%) and demonstrated unilateral disease in the majority of patients (57%), most of which (77%) were undetected by cross-sectional imaging. In patients with resistant hypertension, low renin in the presence of RASi is a strong indicator for autonomous aldosterone secretion. It may serve as an on-medication screening test for PA to select for formal PA work up. What is the context? Primary aldosteronism (PA) is associated with an uncontrolled secretion of the hormone aldosterone and often causes severe forms of high blood pressure. PA is considered the most common cause of high blood pressure which is caused by another medical condition. Medical societies have issued precise recommendations for the screening of this disease, which includes the determination of aldosterone and its main regulator renin. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice. What is the problem? In clinical studies, the determination of renin, aldosterone and its ratio (ARR) proved to be a valid screening tool. Nevertheless, in everyday life assessing and interpreting these results can be challenging for the clinician. The ARR is influenced by all first-line antihypertensives and in case of doubt, an extensive change in medication is recommended. Especially patients with resistant hypertension may require intensive medical care when medication is changed. What is important? In this study, we analysed patients at risk for PA who had inadequate low renin in presence of RASi (ACE inhibitors, Angiotensin receptor blockers). This study suggests that in patients with severe hypertension, the determination of renin in presence of RASi can provide further information on the presence of autonomic aldosterone secretion at a glance. However, this approach cannot and should not replace the algorithm proposed by current guidelines. In contrast, this approach should be an easy-to-implement concept that should prime the initiation of further appropriate diagnostics. [ABSTRACT FROM AUTHOR]

Discrepancies exist between guideline recommendations and real-world practice of blood pressure (BP) measurements. The aim of this study was to assess, with a nationwide, questionnaire-based survey, the current practice of BP measurement and associated BP values in German medical practices. A nationwide survey in German medical practices was performed in the period from 10 May 2021 to 15 August 2021. The questionnaire was divided into five sections. The current office BP (OBP) values as well as the current drug therapy were recorded. In addition, the implementation of office BP (OBP) and home BP monitoring (HBPM) was queried. For analysis, questionnaires were scanned and automatically digitised. A total of 7049 questionnaires were analysed, the majority of which came from general practitioners (66%) and internal medicine practices (34%). The average OBP (SD) was 140.0 (18)/82.7 (11) mmHg. 40.8% of treated patients had OBP in the controlled range, with monotherapy (34.7%) or dual combination therapy (38.2%) prescribed in most cases. OBP was taken from a single measurement in 66.3% of cases, and in 21.8% from 23 measurements. OBP was mostly measured after a rest period (87.1%) and in a separate room (80.4%). HBPM was performed in 62.3% of patients; however, in 24.9% of the participants HBP measurements were recorded once a week or less. In this nationwide survey in German medical practices, BP control remains at below 50%, while monotherapy is prescribed in around one third of patients. Moreover, office measurements and HBPM are often not performed according to current guideline recommendations. What is the context? Elevated blood pressure (hypertension) is an important risk factor for diseases such as stroke or heart attack. However, sufficient drug therapy can significantly reduce the risk of complications such as a stroke. An adequate blood pressure measurement is the basis for diagnostics and successful therapy. In order to measure blood pressure as accurately as possible, recommendations for performing blood pressure measurements (at home as well as in the office) have been published by medical societies. Research suggests that blood pressure is not always measured according to these recommendations. However, there are no current studies for Germany. What is new? In this study, we analysed the results of a survey in which medical practices and pharmacies throughout Germany were asked about blood pressure measurement and blood pressure therapy. The key results of our study suggest that: • The blood pressure of many participants with known hypertension is not within the desired target range. • Office blood pressure measurements are often not performed as suggested by guidelines. This mainly affects time-consuming work steps such as repeating the measurement several times. • Home blood pressure is not recorded in a structured form, as suggested, but rather according to a random pattern by the patient. What is important? This study suggests that blood pressure control is not sufficient in the study participants. Furthermore, blood pressure measurement as an important tool for hypertension management is frequently not performed as proposed by guidelines. [ABSTRACT FROM AUTHOR]

Objective: The long‐term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women. Methods: Twenty‐four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non‐angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood‐derived endothelial colony‐forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models. Results: Kidney transplant recipients displayed a reduced ratio of angiogenic and non‐angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability. Conclusions: Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract: Regeneration of arterial endothelium after injury is critical for the maintenance of normal blood flow, cell trafficking, and vascular function. Using mouse models of carotid injury, we show that the transition from a static to a dynamic phase of endothelial regeneration is marked by a strong increase in endothelial proliferation, which is accompanied by induction of the chemokine CX3CL1 in endothelial cells near the wound edge, leading to progressive recruitment of Ly6Clo monocytes expressing high levels of the cognate CX3CR1 chemokine receptor. In Cx3cr1‐deficient mice recruitment of Ly6Clo monocytes, endothelial proliferation and regeneration of the endothelial monolayer after carotid injury are impaired, which is rescued by acute transfer of normal Ly6Clo monocytes. Furthermore, human non‐classical monocytes induce proliferation of endothelial cells in co‐culture experiments in a VEGFA‐dependent manner, and monocyte transfer following carotid injury promotes endothelial wound closure in a hybrid mouse model in vivo. Thus, CX3CR1 coordinates recruitment of specific monocyte subsets to sites of endothelial regeneration, which promote endothelial proliferation and arterial regeneration. [ABSTRACT FROM AUTHOR]

Carotid stenosis (CS) is an important cause of ischemic stroke. However, reliable markers for the purpose of identification of high-risk, so-called vulnerable carotid plaques, are still lacking. Monocyte subsets are crucial players in atherosclerosis and might also contribute to plaque rupture. In this study we, therefore, aimed to investigate the potential role of monocyte subsets and associated chemokines as clinical biomarkers for vulnerability of CS. Patients with symptomatic and asymptomatic CS (n = 21), patients with cardioembolic ischemic strokes (n = 11), and controls without any cardiovascular disorder (n = 11) were examined. Cardiovascular risk was quantified using the Essen Stroke Risk Score (ESRS). Monocyte subsets in peripheral blood were measured by quantitative flow cytometry. Plaque specimens were histologically analyzed. Furthermore, plasma levels of monocyte chemotactic protein 1 (MCP-1) and fractalkine were measured. Intermediate monocytes (Mon2) were significantly elevated in symptomatic and asymptomatic CS-patients compared to controls. Mon2 counts positively correlated with the ESRS. Moreover, stroke patients showed an elevation of Mon2 compared to controls, independent of the ESRS. MCP-1 levels were significantly higher in patients with symptomatic than in those with asymptomatic CS. Several histological criteria significantly differed between symptomatic and asymptomatic plaques. However, there was no association of monocyte subsets or chemokines with histological features of plaque vulnerability. Due to the multifactorial influence on monocyte subsets, the usability as clinical markers for plaque vulnerability seems to be limited. However, monocyte subsets may be critically involved in the pathology of CS. [ABSTRACT FROM AUTHOR]