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Hypertension is a significant risk factor for cardiovascular disease and mortality worldwide. The kidney is a major regulator of blood pressure and electrolyte homeostasis, with monogenic disorders indicating a link between abnormal ion transport and salt-sensitive hypertension. However, the association between salt and hypertension remains controversial. Thus, there is continued interest in deciphering the molecular mechanisms behind these processes. Uromodulin (UMOD) is the most abundant protein in the normal urine and is primarily synthesized by the thick ascending limb epithelial cells of the kidney. Genome-wide association studies have linked common UMOD variants with kidney function, susceptibility to chronic kidney disease and hypertension independent of renal excretory function. This review will discuss and provide predictions on the role of the UMOD protein in renal ion transport and hypertension based on current observational, biochemical, genetic, pharmacological and clinical evidence., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage. Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words 'hypertension' and 'proteomics', and focused specifically on the most recent literature on the utility of proteomics in hypertension research. Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers. [ABSTRACT FROM AUTHOR]

Differential proteomic technology was used to identify urine proteomic profile of gestational hypertension and preeclampsia. Urine samples were collected from 10 patients with gestational hypertension, 10 patients with mild preeclampsia, 10 patients with severe preeclampsia and 10 normal pregnancies and analyzed by 2-D difference gel electrophoresis, then matrix assisted laser desorption ionization mass spectrometry was used to identify differential proteins. Subsequently, ELISA was used to verify the content variation of the identified proteins in 200 urine samples. In total, 30 differential proteins were identified. For prostaglandin-H2 D-isomerase (L-PGDS), perlecan and other 15 proteins, the contents in patients with gestational hypertension were higher than that of normal pregnancies, but lower in mild and severe preeclampsia. By contrast, serum albumin and α-1-antitrypsin was lower in samples from patients with gestational hypertension and higher in patients with mild and severe preeclampsia compared with normal pregnancies. ELISA verified that the urinary concentration of L-PGDS and perlecan were significantly lower in patients with preeclampsia than in normal pregnancies (P<0.05). Urine proteomics is a useful tool to identify potential biomarkers to distinguish between different types of hypertensive disorders in pregnancy. L-PGDS and perlecan could potentially be used as markers to reflect the state of renal function, and may participate in the genesis and development of renal injury during preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual's blood pressure, the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection, and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases. Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. While there are only few proteomic studies specifically addressing human primary hypertension, there are more data available in hypertensive disorders in pregnancy, such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches. Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardized large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Hypertensive disorders in pregnancy have been the cause of much clinical dilemma, affecting up to 10 % of all pregnancies. The precise blood pressure to achieve in a pregnant woman is usually a battle between minimizing end organ damage to the mother and providing adequate perfusion to the placenta and the fetus. This predicament is becoming more, not less, frequent as maternal ages increase in high resource nations. Biomarkers to predict preeclampsia, a subcategory of hypertension in pregnancy, have always been elusive. The discovery of angiogenic factors relevant to preeclampsia in the last decade, however, has propelled much needed research, both in the basic science and clinical arenas. In this review, we summarize the latest clinical studies and international guidelines on blood pressure goals in pregnancy, and discuss the most promising of biomarkers to predict or diagnose preeclampsia. [ABSTRACT FROM AUTHOR]

The current definition of hypertension is based on blood pressure values, and blood pressure also drives treatment decisions, is the most important treatment monitoring tool and helps estimating risk of hypertension-related organ damage. In an era of precision medicine, additional biomarkers are needed in the diagnosis and management of patients with hypertension. In this review, we outline the areas in which functional, imaging and circulating biomarkers could help in a more individualised definition of hypertension and associated risk. We will cover biomarkers for diagnosis; of patho-physiology and prediction of hypertension; response to treatment, organ damage; and to monitor treatment. A clear focus is on the vasculature, the heart and the kidneys, whereas we see a need to further develop biomarkers of cerebral function in order to diagnose cognition deficits and monitor changes in cognition in the future to support addressing the growing burden of hypertension-associated vascular dementia. [ABSTRACT FROM AUTHOR]

BACKGROUND Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. The incidence of preeclampsia seems to be rising because of increased prevalence of predisposing disorders, such as essential hypertension, diabetes, and obesity, and there is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. METHODS We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive white women, of whom 16 subjects developed preeclampsia. RESULTS We found that structural capillary rarefaction at 20–24 weeks of gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cutoff of 2 capillaries/field with the area under the curve of the receiver operating characteristic value of 0.70, whereas capillary rarefaction at 27–32 weeks of gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cutoff of 8 capillaries/field with area under the curve of the receiver operating characteristic value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariable analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension and in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27–32 weeks. CONCLUSIONS Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia. [ABSTRACT FROM PUBLISHER]

Proteomics, the study of the proteins making up the proteome, has emerged in recent years as an important tool in several different fields of medical research for early disease detection, for assessment of response to treatment and for unravelling underlying pathophysiological mechanisms. Although the majority of patients with hypertension are treated in a similar manner, the causes underlying the condition are diverse, and often poorly understood. Genetic studies have implicated several different candidate genes, but it may be that examination of the 'downstream' products of genes, the proteins, will help to improve understanding of the link between the environmental and genetic effects that contribute towards development of hypertension. Proteomic studies can be performed quickly and reliably on several different sample types including plasma and urine, requiring minimal pre-test preparation. In this review, we will compare the different analytical platforms and technical issues involved in proteomic analysis. We will discuss existing studies of proteomics in hypertension, as well as related conditions such as renal disease, pre-eclampsia and coronary artery disease. We will also explore potential future applications of proteomics-based research, which may ultimately lead to improved population screening, monitoring of therapy and early detection of target organ damage. [ABSTRACT FROM AUTHOR]

Hypertension is a major cardiovascular risk factor with a multifactorial pathogenesis, including genetic and environmental factors. In addition to hypothesis-driven strategies, unbiased approaches such as genomics, proteomics, and metabolomics are useful tools to help unravel the pathophysiology of hypertension and associated organ damage. During development of cardiovascular disease the key organs and tissues undergo extensive functional and structural changes that are characterized by alterations in the amount and type of proteins that are expressed. Proteomic approaches study the expression of large numbers of proteins in organs, tissues, cells, and body fluids. A number of different proteomic platforms are available, many of which combine two methods to separate proteins and peptides after an initial digestion step. Identification of these peptides and changes in their expression in parallel with disease processes or medical treatment will help to identify as yet unknown pathophysiological pathways. There is also potential to use proteomic signatures as biomarkers of cardiovascular disease that will contribute to population screening, diagnosis of diseases and their severity, and monitoring of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Hypertension is the most common medical disorder encountered during pregnancy. A recent report highlighted hypertensive disorders as one of the major causes of pregnancy-related maternal deaths in the United States. Significant advances in our understanding of preeclampsia, a form of hypertension unique to pregnancy, have occurred in recent years. The optimal timing and choice of therapy for hypertensive pregnancy disorders involves carefully weighing the risk-versus-benefit ratio for each individual patient, with an overall goal of improving maternal and fetal outcomes. In this review, we summarize the mechanisms thought to be involved, review the current management guidelines for hypertensive pregnancy disorders as recommended by international guideline groups, and outline some newer perspectives on management. [ABSTRACT FROM AUTHOR]

Around 20% of all deliveries are preceded by labour induction, a proportion that has not varied dramatically over recent years. Fetal death was the only indication for labour induction centuries ago, while this is now a very rare indication, with prolonged pregnancy and maternal hypertensive disorders being the major indications for the last 50-60 years. Techniques for inducing labour have also changed from dietary delicacies and verbal threats giving way to physical stimulation mainly achieved by cervical stretching and amniotomy and more recently to sophisticated pharmacological manipulation using oxytocin and prostaglandins, based on our expanding knowledge of the physiological processes involved in spontaneous parturition. Relaxin, antiprogestins, nitric oxide as well as complementary medicines have also been explored in recent years. Successful induction is, however, still not guaranteed and there has been increasing emphasis during the past decade on exploring strategies for identifying the probability of success. Measurement of fetal fibronectin in cervical mucus, maternal serum nitrite/nitrate concentrations, ultrasound delineation of cervical form and electrical impedance measurements across the cervix are all being investigated. Safety, success, and patient satisfaction continue to be the major objectives with economic evaluations now becoming a significant factor in the search for the ideal induction method. [ABSTRACT FROM AUTHOR]