Endothelial-to-mesenchymal transition (EndMT) is a process that encompasses extensive transcriptional reprogramming of activated endothelial cells leading to a shift toward mesenchymal cellular ...phenotypes and functional responses. Initially observed in the context of embryonic development, in the last few decades EndMT is increasingly recognized as a process that contributes to a variety of pathologies in the adult organism. Within the settings of cardiovascular biology, EndMT plays a role in various diseases, including atherosclerosis, heart valvular disease, cardiac fibrosis, and myocardial infarction. EndMT is also being progressively implicated in development and progression of pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH). This review covers the current knowledge about EndMT in PH and PAH, and provides comprehensive overview of seminal discoveries. Topics covered include evidence linking EndMT to factors associated with PAH development, including hypoxia responses, inflammation, dysregulation of bone-morphogenetic protein receptor 2 (BMPR2), and redox signaling. This review amalgamates these discoveries into potential insights for the identification of underlying mechanisms driving EndMT in PH and PAH, and discusses future directions for EndMT-based therapeutic strategies in disease management.
Introduction: Pulmonary arterial hypertension (PAH) frequently requires administration of prostacyclin analogs using either a continuous SQ infusion pump or an inhalation device. Discussion: A recent ...phase III study ("GRIPHON") included 1156 randomized patients to selexipag which reduced the risk of morbidity/mortality events by 40% (HR=0.6, 99% CI: 0.46-0.78, p<0.0001) and was associated with improvement in hemodynamics.
Liver disease and portal hypertension can be associated with pulmonary vascular complications, including portopulmonary hypertension (POPH), characterised by an elevated mean pulmonary artery ...pressure secondary to an increased pulmonary vascular resistance, and hepatopulmonary syndrome (HPS), characterised by hypoxaemia due to pulmonary vasodilatation and shunting. Although clear diagnostic guidelines exist for both conditions on the basis of echocardiography, right heart catheterisation and arterial blood gases, there is considerable variation between centres regarding diagnosis and management of these conditions. Awareness of evaluation and management algorithms for POPH and HPS are critical for optimisation of outcomes in patients with these conditions. Key aspects of management of POPH and HPS include identification of patients likely to benefit from liver transplantation (LTx) and management before and after LTx. Although both disorders may improve after LTx, severe forms of POPH represent a contraindication to LTx. Novel approaches to the treatment of POPH and HPS offer new management options that may expand the pool of transplantable patients and improve overall outcomes.
Blood pressure related to age: The India ABPM study Kaul, Upendra; Omboni, Stefano; Arambam, Priyadarshini ...
The journal of clinical hypertension (Greenwich, Conn.),
December 2019, Letnik:
21, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The present paper reports trends in office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) with age in a large multi‐center Indian all comers’ population ...visiting primary care physicians. ABPM and OBPM data from 27 472 subjects (aged 51 ± 14 years, males 68.2%, treated 45.5%) were analyzed and compared. Individual differences between OBPM and ABPM patterns were compared for patients according to 10‐year age categories. Results showed that systolic (S) BP values started to increase with age from the age of 40, BP variability (SD) increased from the age of 30 years. Diastolic (D) BP values started to decrease from the age of 50 years. Mean OBPM values were higher than daytime ABPM values (all P < .001) in all age‐groups. The prevalence of white coat hypertension (WCH) and masked hypertension (MH) was based on OBPM and daytime, 24‐hour, and nighttime average BPs together. WCH decreased with age from 15.1% and 12.4% in treated and untreated subjects at the youngest age to 7.2% and 6.9% in the oldest age, respectively. MH prevalence was higher for untreated than for treated subjects but remained similar for all age‐groups (range of 18.6%‐21.3%). The prevalence of reverse dippers increased with age from the youngest to oldest group with 7.3%‐34.2% (P < .001 for trend). Dippers prevalence decreased from 42.5% to 17.9% from the youngest to oldest age‐groups, respectively (P < .001 for trend). These findings confirm that BP patterns show clear differences in trends with age, particularly regarding nighttime BP.
Abstract
BACKGROUND
Interleukin-11 (IL-11) is a pleiotropic cytokine of the interleukin-6 family. Recent studies revealed its crucial role in the development of cardiovascular fibrosis. In this study ...we examined IL-11 expression levels in the heart and the kidney exposed to high blood pressure in renovascular hypertensive rats and their correlations to fibrotic markers and kidney injury.
METHODS
Two-kidney, one-clip renovascular hypertension (2K1C) was induced in rats. IL-11 expression was measured by real-time polymerase chain reaction in the left ventricle and the right kidney. The correlation of cardiac IL-11 expression with biomarkers of renal fibrosis was assessed. We further investigated IL-11 expression in 2K1C rats grouped into rats with malignant vs. nonmalignant hypertension (distinguishing criteria: weight loss, number of fibrinoid necrosis, and onion skin lesions).
RESULTS
Thirty-five days after clipping, mean arterial pressure was significantly increased in 2K1C. Renal IL-11 expression was elevated in 2K1C. In the heart there was only a trend toward higher IL-11 expression in 2K1C. IL-11 in the kidney in 2K1C correlated with the expression of transforming growth factor (TGF)-β1/2, collagens, fibronectin, osteopontin, as well as tissue inhibitors of metalloprotease 1/2. There were also correlations of IL-11 with tissue collagen expansion, number of activated fibroblasts and serum creatinine, but no correlation with mean arterial pressure. Renal expression of IL-11 was highest in rats with malignant hypertension.
CONCLUSIONS
Renal IL-11 expression of renovascular hypertensive rats is markedly increased and correlates with profibrotic markers and loss of function and might therefore serve as a biomarker for the severity of hypertensive nephrosclerosis.
Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of ...Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.
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