Nano guardians of the heart: A comprehensive investigation into the impact of silver nanoparticles on cardiovascular physiology.

Globally, cardiovascular diseases (CVDs) constitute the leading cause of death at the moment. More effective treatments to combat CVDs are urgently required. Recent advances in nanotechnology have opened the door to new avenues for cardiovascular health treatment. Silver nanotechnology's inherent therapeutic powers and wide-ranging applications have made it the center of focus in recent years. This review aims to analyze the chemical, physical, and biological processes ofproducing AgNPs and determine their potential utility as theranostics. Despite significant advances, the precise mechanism by which AgNPs function in numerous biological systems remains a mystery. We hope that at the end of this review, you will better understand how AgNPs affect the cardiovascular system from the research done thus far. This endeavor thoroughly investigates the possible toxicological effects and risks associated with exposure to AgNPs. The findings shed light on novel applications of these versatile nanomaterials and point the way toward future research directions. Due to a shortage of relevant research, we will limit our attention to AgNPs as they pertain to CVDs. Future research can use this opportunity to investigate the many medical uses of AgNPs. Given their global prevalence, we fully endorse academics' efforts to prioritize nanotechnological techniques in pursuing risk factor targeting for cardiovascular diseases. The critical need for innovative solutions to this widespread health problem is underscored by the fact that this technique may help with the early diagnosis and treatment of CVDs.

Analyzing the use of proton pump inhibitors in elite athletes: understanding the impact on cardiovascular health and performance

Objective: To assess the impact of proton pump inhibitors (PPIs) on cardiovascular health and performance in elite athletes. This study aims to understand the utilization patterns, potential cardiovascular implications, and performance outcomes associated with PPI use in this specific population. Methods: A comprehensive review of PPI use among elite athletes was conducted, including a detailed analysis of medication type, dosage, frequency, and duration. The study involved a retrospective examination of medical and training records of athletes whoused PPIs in 2021. The analysis focused on evaluating the correlation between PPI use and cardiovascular health markers, as well as performance metrics in these athletes. Results: The study found a significant prevalence of PPI use among elite athletes, primarily for managing exercise-induced gastrointestinal symptoms. Key findings include: (1) a notable variation in the type and dosage of PPIs used; (2) a correlation between long-term PPI use and certain cardiovascular health markers; (3) athletes on PPIshad varied performance outcomes, with some showing decreased endurance. Conclusion: The study highlights the need for a more nuanced understanding of PPI use in elite athletes, emphasizing the importance of personalized medical guidance. While PPIs can bebeneficial for managing specific gastrointestinal issues in athletes, their impact on cardiovascular health and athletic s requires careful consideration and monitoring. This research underscores the necessity for developing tailored medication strategiesfor elite athletes to optimize health and performance outcomes (AU)

Xanthine oxidase mediates chronic stress-induced cerebrovascular dysfunction and cognitive impairment.

Xanthine oxidase (XO) mediates vascular function. Chronic stress impairs cerebrovascular function and increases the risk of stroke and cognitive decline. Our study determined the role of XO on stress-induced cerebrovascular dysfunction and cognitive decline. We measured middle cerebral artery (MCA) function, free radical formation, and working memory in 6-month-old C57BL/6 mice who underwent 8 weeks of control conditions or unpredictable chronic mild stress (UCMS) with or without febuxostat (50 mg/L), a XO inhibitor. UCMS mice had an impaired MCA dilation to acetylcholine vs. controls (p < 0.0001), and increased total free radical formation, XOR protein levels, and hydrogen peroxide production in the liver compared to controls. UCMS increased hydrogen peroxide production in the brain and cerebrovasculature compared to controls. Working memory, using the y-maze test, was impaired (p < 0.05) in UCMS mice compared to control mice. However, blocking XO using febuxostat prevented the UCMS-induced impaired MCA response, while free radical production and hydrogen peroxide levels were similar to controls in the liver and brain of UCMS mice treated with febuxostat. Further, UCMS + Feb mice did not have a significant reduction in working memory. These data suggest that the cerebrovascular dysfunction associated with chronic stress may be driven by XO, which leads to a reduction in working memory.

Trending Nutrition Controversies #3: Top Controversies in 2021.

Each year, patients are bombarded with diverging and even contradictory reports concerning the impact of certain additives, foods, and nutrients on cardiovascular health and its risk factors. Accordingly, this third review of nutrition controversies examines the impact of artificial sweeteners, cacao, soy, plant-based meats, nitrates, and meats from grass compared to grain-fed animals on cardiovascular and other health outcomes with the goal of optimizing clinician-led diet counseling.

Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor.

2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development.

Alcohol's Impact on the Cardiovascular System.

Alcohol consumption has been shown to have complex, and sometimes paradoxical, associations with cardiovascular diseases (CVDs). Several hundred epidemiological studies on this topic have been published in recent decades. In this narrative review, the epidemiological evidence will be examined for the associations between alcohol consumption, including average alcohol consumption, drinking patterns, and alcohol use disorders, and CVDs, including ischaemic heart disease, stroke, hypertension, atrial fibrillation, cardiomyopathy, and heart failure. Methodological shortcomings, such as exposure classification and measurement, reference groups, and confounding variables (measured or unmeasured) are discussed. Based on systematic reviews and meta-analyses, the evidence seems to indicate non-linear relationships with many CVDs. Large-scale longitudinal epidemiological studies with multiple detailed exposure and outcome measurements, and the extensive assessment of genetic and confounding variables, are necessary to elucidate these associations further. Conflicting associations depending on the exposure measurement and CVD outcome are hard to reconcile, and make clinical and public health recommendations difficult. Furthermore, the impact of alcohol on other health outcomes needs to be taken into account. For people who drink alcohol, the less alcohol consumed the better.

Selenium, a Micronutrient That Modulates Cardiovascular Health via Redox Enzymology.

Selenium (Se) is a trace nutrient that promotes human health through its incorporation into selenoproteins in the form of the redox-active amino acid selenocysteine (Sec). There are 25 selenoproteins in humans, and many of them play essential roles in the protection against oxidative stress. Selenoproteins, such as glutathione peroxidase and thioredoxin reductase, play an important role in the reduction of hydrogen and lipid hydroperoxides, and regulate the redox status of Cys in proteins. Emerging evidence suggests a role for endoplasmic reticulum selenoproteins, such as selenoproteins K, S, and T, in mediating redox homeostasis, protein modifications, and endoplasmic reticulum stress. Selenoprotein P, which functions as a carrier of Se to tissues, also participates in regulating cellular reactive oxygen species. Cellular reactive oxygen species are essential for regulating cell growth and proliferation, protein folding, and normal mitochondrial function, but their excess causes cell damage and mitochondrial dysfunction, and promotes inflammatory responses. Experimental evidence indicates a role for individual selenoproteins in cardiovascular diseases, primarily by modulating the damaging effects of reactive oxygen species. This review examines the roles that selenoproteins play in regulating vascular and cardiac function in health and disease, highlighting their antioxidant and redox actions in these processes.

Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling.

Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.

Caffeine during High-Intensity Whole-Body Exercise: An Integrative Approach beyond the Central Nervous System.

Caffeine is one of the most consumed ergogenic aids around the world. Many studies support the ergogenic effect of caffeine over a large spectrum of exercise types. While the stimulatory effect of caffeine on the central nervous system is the well-accepted mechanism explaining improvements in exercise performance during high-intensity whole-body exercise, in which other physiological systems such as pulmonary, cardiovascular, and muscular systems are maximally activated, a direct effect of caffeine on such systems cannot be ignored. A better understanding of the effects of caffeine on multiple physiological systems during high-intensity whole-body exercise might help to expand its use in different sporting contexts (e.g., competitions in different environments, such as altitude) or even assist the treatment of some diseases (e.g., chronic obstructive pulmonary disease). In the present narrative review, we explore the potential effects of caffeine on the pulmonary, cardiovascular, and muscular systems, and describe how such alterations may interact and thus contribute to the ergogenic effects of caffeine during high-intensity whole-body exercise. This integrative approach provides insights regarding how caffeine influences endurance performance and may drive further studies exploring its mechanisms of action in a broader perspective.

The Potential Role of Creatine in Vascular Health.

Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health.

Regulatory role of endogenous and exogenous fibroblast growth factor 1 in the cardiovascular system and related diseases.

Fibroblast growth factor 1 (FGF1) has a critical regulatory role in the development of the cardiovascular system (CVS) and is strongly associated with the progression or treatment of cardiovascular diseases (CVDs). However, the regulatory mechanisms of FGF1 in CVS and CVDs have not yet been fully elucidated. Therefore, this review article summarized the existing literature reports on the role of FGF1 in CVS under physiological and pathological conditions. First, the expression and physiological functions of endogenous FGF1 is fully demonstrated. Then, we analyzed the role of exogenous FGF1 in normal CVS and related pathological processes. Specifically, the potential signaling pathways might be mediated by FGF1 in CVDs treatment is discussed in detail. In addition, the barriers and feasible solutions for the application of FGF1 are further analyzed. Finally, we highlight therapeutic considerations of FGF1 for CVDs in the future. Thus, this article may be as a reference to provide some ideas for the follow-up research.

Caloric restriction, physical exercise, and CB1 receptor blockade as an efficient combined strategy for bodyweight control and cardiometabolic status improvement in male rats.

Obesity is critically associated with the development of insulin resistance and related cardiovascular and kidney diseases. Several strategies for weight loss have been developed but most of them exhibit a post-intervention rebound effect. Here, we aimed to design combined weight-loss strategies of caloric restriction, physical exercise, and administration of a CB1 receptor blocker to inhibit food intake that also accomplish the objectives of lost-weight maintenance and improvement of cardiovascular and renal function. Diet-induced obesity (DIO) was generated in Sprague Dawley rats for 12 weeks to test the effects of single or combined strategies (i.e. caloric restriction, mixed training protocol, and/or administration of appetite suppressant) on caloric intake, body weight, cardiovascular and renal functionality resulting from a weight-loss intervention period of 3 weeks followed by 6 weeks of weight maintenance. Consumption of a high-fat diet (HFD) caused a significant increase in body weight (5th week of the experimental period) and led to the development of insulin resistance, cardiovascular, and renal alterations. The different interventions tested, resulted in a significant body weight loss and improved glucose metabolism, aerobic capacity, electrocardiographic parameters, vascular expression of adhesion molecules and inflammatory mediators, and renal functionality, reaching values similar to the control normocaloric group or even improving them. Successful maintenance of lost weight was achieved along a 6-week maintenance period in addition to adequate health status. In conclusion, the weight-loss and maintenance intervention strategies tested were efficient at reversing the obesity-related alterations in body weight, glucose metabolism, aerobic capacity, cardiovascular and renal functionality. The beneficial action was very consistent for caloric restriction and physical exercise, whereas administration of a CB1 receptor blocker complemented the effects of the prior interventions in some parameters like body weight or aerobic capacity, and showed specific actions in renal status, increasing glomerular filtration rate and diuresis. Overall, the novelty of our study relies on the easy implementation of combined strategies for effective weight management that resulted in significant health benefits.

Smoking flies: testing the effect of tobacco cigarettes on heart function of Drosophila melanogaster.

Studies about the relationship between substances consumed by humans and their impact on health, in animal models, have been a challenge due to differences between species in the animal kingdom. However, the homology of certain genes has allowed extrapolation of certain knowledge obtained in animals. Drosophila melanogaster, studied for decades, has been widely used as model for human diseases as well as to study responses associated with the consumption of several substances. In the present work we explore the impact of tobacco consumption on a model of 'smoking flies'. Throughout these experiments, we aim to provide information about the effects of tobacco consumption on cardiac physiology. We assessed intracellular calcium handling, a phenomenon underlying cardiac contraction and relaxation. Flies chronically exposed to tobacco smoke exhibited an increased heart rate and alterations in the dynamics of the transient increase of intracellular calcium in myocardial cells. These effects were also evident under acute exposure to nicotine of the heart, in a semi-intact preparation. Moreover, the alpha 1 and 7 subunits of the nicotinic receptors are involved in the heart response to tobacco and nicotine under chronic (in the intact fly) as well as acute exposure (in the semi-intact preparation). The present data elucidate the implication of the intracellular cardiac pathways affected by nicotine on the heart tissue. Based on the probed genetic and physiological similarity between the fly and human heart, cardiac effects exerted by tobacco smoke in Drosophila advances our understanding of the impact of it in the human heart. Additionally, it may also provide information on how nicotine-like substances, e.g. neonicotinoids used as insecticides, affect cardiac function.This article has an associated First Person interview with the first author of the paper.

14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial.

CONTEXT: Postprandial hyperglycemia increases systemic inflammation and is a risk factor for cardiovascular disease. A ketone monoester (KME) drink containing ß-hydroxybutyrate (ß-OHB) rapidly lowers plasma glucose, which may be a strategy protecting against postprandial hyperglycemia. OBJECTIVE: We hypothesized that KME would attenuate 2-hour postprandial glucose, lower systemic inflammation, and improve vascular function in adults with obesity. METHODS: In a randomized crossover design, 14 participants with obesity (age = 56 ±â€…12 years; body mass index = 32.8 ±â€…7.7 kg/m2) consumed KME (12 g ß-OHB) or placebo 15 minutes prior to each meal for 14 days with all meals provided and matched between conditions. Postprandial glycemia was assessed by continuous glucose monitoring. Vascular function and inflammation were assessed before and after treatment periods. RESULTS: Postprandial glucose was 8.0% lower in KME versus placebo (g = 0.735; P = 0.011) and 24-hour average glucose reduced by 7.8% (g = 0.686; P = 0.0001). Brachial artery flow-mediated dilation increased from 6.2  ±â€… 1.5% to 8.9 ±â€…3.3% in KME (g = 1.05; P = 0.0004) with no changes in placebo (condition × time interaction, P = 0.004). There were no changes in plasma cytokines; however, lipopolysaccharide-stimulated monocyte caspase-1 activation was lower following KME supplementation versus placebo (stimulation × condition × time interaction; P = 0.004). The KME supplement was well tolerated by participants and adherence to the supplementation regimen was very high. CONCLUSIONS: In adults with obesity, 14 days of premeal KME supplementation improves glucose control, enhances vascular function, and may reduce cellular inflammation. KME supplementation may be a viable, nonpharmacological approach to improving and protecting vascular health in people with heightened cardiometabolic risk.

Adrenergic receptors and cardiovascular effects of catecholamines.

Activation of the sympathetic nervous system is responsible for the body's "fight or flight" reaction. The physiological responses to the activation of the sympathetic nervous system and adrenal medulla are mediated through the action of the endogenous catecholamines norepinephrine (or noradrenaline) and epinephrine (or adrenaline) on adrenergic receptors. Adrenergic receptors belong to the superfamily of G protein-coupled receptors (GPCR). Adrenoceptors are divided into alpha1, alpha2, beta1, beta2 and beta3 receptors. Norepinephrine stimulates both subtypes of α receptors and ß1 receptors. Epinephrine stimulates all subtypes ofα and ß adrenoreceptors. α1 adrenergic receptors, coupled to stimulatory Gq proteins, activate the enzyme phospholipase C and are mainly found in the smooth muscle cells of blood vessels and urinary tract, where they induce constriction. α2 receptors are coupled to inhibitory Gi proteins, that inactivate adenylyl cyclase, decreasing cyclic adenosine monophosphate (AMP) production. They are mainly found in the central nervous system, where their activation results in a decreased arterial blood pressure. ß1 adrenoreceptors predominate in the heart, activate the Gs-adenylyl cyclase -cAMP-protein kinase A signaling cascade, and induce positive inotropic and chronotropic effects. ß2 adrenoreceptors are distributed extensively throughout the body, but are expressed predominantly in bronchial smooth muscle cells. ß2 adrenergic receptors activate adenylyl cyclase, dilate blood vessels and bronchioles, relax the muscles of the uterus, bladder and gastrointestinal duct, and also decrease platelet aggregation and glycogenolysis. ß3 receptors can couple interchangeably to both stimulating and inhibiting G proteins. They are abundantly expressed in white and brown adipose tissue, and increase fat oxidation, energy expenditure and insulin-mediated glucose uptake. This review details the regulation of cardiac and vascular function by adrenergic receptors.

Role of Nicotinic Acetylcholine Receptors in Cardiovascular Physiology and Pathophysiology: Current Trends and Perspectives.

Nicotinic acetylcholine receptors (nAChRs) comprise a large family of ligand-gated ion channels that have a broad distribution in neurons and non-neuronal cells throughout the body. Native nAChRs, activated by acetylcholine (ACh) endogenously, are involved in a variety of physiological and pathophysiological processes. They regulate processes necessary for network operations through neurotransmitter release, cell excitability and neuronal integration. Emerging evidence suggests that nAChRs are capable of regulating cardiovascular (CV) functions in a cell type-specific manner, through the nervous system and non-neuronal tissues. The aim of this review is to describe the most recent findings regarding the role of nAChRs inside and outside the nervous system in the regulation of CV activities.

Platinum accumulation in the brain and alteration in the central regulation of cardiovascular and respiratory functions in oxaliplatin-treated rats.

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. Neurotoxicity is one of its major adverse effects that often demands dose limitation. However, the effects of chronic oxaliplatin on the toxicity of the autonomic nervous system regulating cardiorespiratory function and adaptive reflexes are unknown. Male Sprague Dawley rats were treated with intraperitoneal oxaliplatin (3 mg kg-1 per dose) 3 times a week for 14 days. The effects of chronic oxaliplatin treatment on baseline mean arterial pressure (MAP); heart rate (HR); splanchnic sympathetic nerve activity (sSNA); phrenic nerve activity (PNA) and its amplitude (PNamp) and frequency (PNf); and sympathetic reflexes were investigated in anaesthetised, vagotomised and artificially ventilated rats. The same parameters were evaluated after acute oxaliplatin injection, and in the chronic treatment group following a single dose of oxaliplatin. The amount of platinum in the brain was determined with atomic absorption spectrophotometry. Chronic oxaliplatin treatment significantly increased MAP, sSNA and PNf and decreased HR and PNamp, while acute oxaliplatin had no effects. Platinum was accumulated in the brain after chronic oxaliplatin treatment. In the chronic oxaliplatin treatment group, further administration of a single dose of oxaliplatin increased MAP and sSNA. The baroreceptor sensitivity and somatosympathetic reflex were attenuated at rest while the sympathoexcitatory response to hypercapnia was increased in the chronic treatment group. This is the first study to reveal oxaliplatin-induced alterations in the central regulation of cardiovascular and respiratory functions as well as reflexes that may lead to hypertension and breathing disorders which may be mediated via accumulated platinum in the brain.

Acute effects of acetaminophen on the developmental, swimming performance and cardiovascular activities of the African catfish embryos/larvae (Clarias gariepinus).

Acetaminophen is a widely used analgesic that has been detected in many water bodies with few reports concerning its potential toxicity to fish. This study sought to assess the developmental, swimming performance and cardiovascular activities of embryo/larvae catfish (Clarias gariepinus) exposed to acetaminophen. The Organization for Economic Development (OECD) Fish Embryo Acute Toxicity Test (OECD 236) was employed. Fertilized embryo were exposed to different concentrations of acetaminophen (0, 0.5, 1, 10 µg/L) for 96 h. Hatching rates of the embryo were observed to decrease with increasing concentrations of acetaminophen. Fish embryo exposed to acetaminophen displayed varying levels of teratogenic effects at different levels of development in a dose-dependent manner. The results also showed a significant (p < 0.05) dose-dependent increase in swimming speed and movement patterns in fish larvae exposed to acetaminophen, with distance travelled in larvae exposed to the highest concentration of acetaminophen (10 µg/L) about eight (8) times the distance travelled by the control larvae, indicating that acetaminophen-induced erratic swimming behaviour in the catfish species. Cardiotoxicity was evident, with a significant reduction in heartbeat rate with increasing concentrations of acetaminophen. The results showed that exposure to acetaminophen resulted in teratogenic, neurotoxic and cardiotoxic effects in embryo/larvae of Clarias gariepinus. The findings suggest that acetaminophen which has recently been detected in many water bodies could potentially impact on survival of aquatic life, especially catfish.

Glycemic Variability and CNS Inflammation: Reviewing the Connection.

Glucose is the primary energy source for the brain, and exposure to both high and low levels of glucose has been associated with numerous adverse central nervous system (CNS) outcomes. While a large body of work has highlighted the impact of hyperglycemia on peripheral and central measures of oxidative stress, cognitive deficits, and vascular complications in Type 1 and Type 2 diabetes, there is growing evidence that glycemic variability significantly drives increased oxidative stress, leading to neuroinflammation and cognitive dysfunction. In this review, the latest data on the impact of glycemic variability on brain function and neuroinflammation will be presented. Because high levels of oxidative stress have been linked to dysfunction of the blood-brain barrier (BBB), special emphasis will be placed on studies investigating the impact of glycemic variability on endothelial and vascular inflammation. The latest clinical and preclinical/in vitro data will be reviewed, and clinical/therapeutic implications will be discussed.

Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):: A Randomized Double-Blind Placebo-Controlled Feasibility Trial.

Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months' treatment with enalapril to improve postnatal cardiovascular function. Echocardiography and hemodynamic measurements were performed at baseline (<3 days), 6 weeks, and 6 months postdelivery on 60 women. At randomization, 88% of women had diastolic dysfunction, and 68% had concentric remodeling/hypertrophy. No difference was seen in total vascular resistance (P=0.59) or systolic function (global longitudinal strain: P=0.14) between groups at 6 months. However, women treated with enalapril had echocardiographic measurements consistent with improved diastolic function (E/E'[the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]: P=0.04) and left ventricular remodeling (relative wall thickness: P=0.01; left ventricular mass index: P=0.03) at 6 months, compared with placebo. Urinary enalapril was detectable in 85% and 63% of women in the enalapril arm at 6 weeks and 6 months, respectively. All women responded positively to taking enalapril in the future. Our study confirmed acceptability and feasibility of the study protocol with a recruitment to completion rate of 2.2 women per month. Importantly, postnatal enalapril treatment was associated with improved echocardiographic measurements; these early improvements have the potential to reduce long-term cardiovascular disease risk. A definitive, multicenter randomized controlled trial is now required to confirm these findings. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT03466333.