BACKGROUND:Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. Activating transcription factor (ATF) 3 has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 (activating transcription factor 3) in AAA development

BACKGROUND:Neutrophil extracellular traps (NETs) are composed of nDNA, enzymes, and citrullinated histones that are expelled by neutrophils in the process of NETosis. NETs accumulate in the aorta and kidneys in hypertension. PAD4 (protein-arginine deiminase-4) is a calcium-dependent enzyme that is essential for NETosis. TRPV4 (transient receptor potential cation channel subfamily V member 4) is a mechanosensitive

Our actions shape the world we live in. In turn, our natural, built, and social conditions shape our health. In recent years, the impact of environmental hazards on human health has emerged as an area of growing concern and intensive study. Among the various health issues linked to environmental factors, cardiovascular diseases are particularly notable due to their prevalence and their status as the

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a

As global temperatures rise, extreme heat events are projected to become more frequent and intense. Extreme heat causes a wide range of health effects, including an overall increase in morbidity and mortality. It is important to note that while there is sufficient epidemiological evidence for heat-related increases in all-cause mortality, evidence on the association between heat and cause-specific

Epidemiological studies have found that transportation noise increases the risk for cardiovascular morbidity and mortality, with solid evidence for ischemic heart disease, heart failure, and stroke. According to the World Health Organization, at least 1.6 million healthy life years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening

Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and cardiovascular risk have garnered the most headlines and are strong, but less attention has been paid to other omnipresent toxicants in our ecosystem. Perfluoroalkyl and polyfluoroalkyl substances

Heavy metals are harmful environmental pollutants that have attracted widespread attention due to their health hazards to human cardiovascular disease. Heavy metals, including lead, cadmium, mercury, arsenic, and chromium, are found in various sources such as air, water, soil, food, and industrial products. Recent research strongly suggests a connection between cardiovascular disease and exposure to

Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality. Other evidence may support physical activity, dietary

As the leading cause of death in the United States, managing coronary heart disease (CHD) is not only a critical objective of the health care system but also a source of resource utilization. With the United States emitting a quarter of the world’s health care-related carbon footprint, the impact of health care access on travel-related carbon emissions must also be examined.1,2 Thus, we investigated

Evidence indicates that living in areas of high greenness is associated with lower rates of cardiovascular and all-cause mortality.1 However, specific health-promoting characteristics of greenness have not been identified, and how greenness interacts with the surrounding ecology to promote human health remains unclear. Identifying the vegetation type, characteristics, and extent of greenness that is

Exposure to ambient fine particulate matter (PM2.5) is associated with increased risk for cardiovascular events and accelerated progression of cardiovascular disease.1 Though substantive advancements have identified plausible mechanistic pathways, critical questions remain unanswered. Previously, we found that exposure to concentrated ambient PM2.5 (CAP) for 30 days increased red blood cell distribution

Derived from the physicochemical degradation of disposed polymers or synthesized for commercial purposes, plastic particles of the microscales or nanoscales have become widespread environmental contaminants, finding their way into water supplies and the food chain. Human exposure to these particles through inhalation, ingestion, or absorption is inevitable, and this is evidenced by their detection

Environmental stressors associated with human activities (eg, air and noise pollution, light disturbance at night) and climate change (eg, heat, wildfires, extreme weather events) are increasingly recognized as contributing to cardiovascular morbidity and mortality. These harmful exposures have been shown to elicit changes in stress responses, circadian rhythms, immune cell activation, and oxidative

BACKGROUND:Preclinical studies have shown the therapeutic potential of VEGF-B (vascular endothelial growth factor B) in revascularization of the ischemic myocardium, but the associated cardiac hypertrophy and adverse side effects remain a concern. To understand the importance of endothelial proliferation and migration for the beneficial versus adverse effects of VEGF-B in the heart, we explored the

BACKGROUND:While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood.METHODS:Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in nearly 19 000 single cells isolated

BACKGROUND:The precise origin of newly formed ACTA2+ (alpha smooth muscle actin-positive) cells appearing in nonmuscularized vessels in the context of pulmonary hypertension is still debatable although it is believed that they predominantly derive from preexisting vascular smooth muscle cells (VSMCs).METHODS:Gli1Cre-ERT2; tdTomatoflox mice were used to lineage trace GLI1+ (glioma-associated oncogene

BACKGROUND:Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension.METHODS:To test this hypothesis, we studied CypD

BACKGROUND:Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression;

BACKGROUND:Hypertension is characterized by CD8+ T cell activation and infiltration into peripheral tissues. CD8+ T cell activation requires proteasomal processing of antigenic proteins. It has become clear that isoLG (isolevuglandin)-adduced peptides are antigenic in hypertension; however, IsoLGs inhibit the constitutive proteasome. We hypothesized that immunoproteasomal processing of isoLG-adducts

BACKGROUND:The resiliency of embryonic development to genetic and environmental perturbations has been long appreciated; however, little is known about the mechanisms underlying the robustness of developmental processes. Aberrations resulting in neonatal lethality are exemplified by congenital heart disease arising from defective morphogenesis of pharyngeal arch arteries (PAAs) and their derivatives

BACKGROUND:During myocardial ischemia/reperfusion (I/R) injury, high levels of matrix Ca2+ and reactive oxygen species (ROS) induce the opening of the mitochondrial permeability transition pore (mPTP), which causes mitochondrial dysfunction and ultimately necrotic death. However, the mechanisms of how these triggers individually or cooperatively open the pore have yet to be determined.METHODS:Here

Dr Kajsa Arkelius completed her Ph.D. in Experimental Vascular Research from the Applied Neurovascular Research group at the University of Lund, Sweden, under the guidance of Dr Saema Ansar. Her doctoral research primarily focused on developing innovative therapeutic approaches to enhance thrombolysis therapy following ischemic stroke. Currently, Dr Arkelius is a postdoctoral fellow in Neurology at

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression

In the article by Kim et al, “Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery,” which published in the March 15, 2024 issue of the journal (Circ Res. 2023;134:727-747. doi: 10.1161/CIRCRESAHA.123.323521), a correction was needed. There is an error in Figure 3 where the descriptions of the solid line and the dotted line are inaccurate and have therefore been removed from the figure footnote

Eliminating the blood clot responsible for an ischemic stroke can improve a patient’s outcome, even save their life. But, the treatment—an intravenous dose of tissue plasminogen activator (rt-PA)—can only be given in the first few hours of symptoms. After that, the risk of hemorrhage associated with rt-PA is no longer offset by its benefits. Increased matrix metalloprotease 9 (MMP-9), which breaks

BACKGROUND:GPCRs (G-protein-coupled receptors) play a central role in the regulation of smooth muscle cell (SMC) contractility, but the function of SMC-expressed orphan GPCR class C group 5 member C (GPRC5C) is unclear.OBJECTIVE:The aim of this project is to define the role of GPRC5C in SMC in vitro and in vivo.METHODS AND RESULTS:We studied the role of GPRC5C in the regulation of SMC contractility

BACKGROUND:Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown.METHODS:In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes

BACKGROUND:Endothelial activation promotes the release of procoagulant extracellular vesicles and inflammatory mediators from specialized storage granules. Endothelial membrane exocytosis is controlled by phosphorylation. We hypothesized that the absence of PTP1B (protein tyrosine phosphatase 1B) in endothelial cells promotes venous thromboinflammation by triggering endothelial membrane fusion and

BACKGROUND:Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown.METHODS:In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related

A high-fiber diet is believed to reduce a person’s likelihood of developing type 2 diabetes, but it isn’t clear how. Since dietary fiber is not digested by human enzymes, Wang and colleagues hypothesized that fiber-eating gut microbes might be involved. To find out, the team examined diet data, fecal microbiomes, serum metabolites and markers of diabetes in thousands of participants. The analyses revealed

Dr Zheng Wang is a Research Assistant Professor in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine, Bronx, New York. Dr Wang earned his PhD in microbiology from The Chinese University of Hong Kong. He completed his postdoctoral training in Microbiome and Microbial Genomics at Columbia University Medical Center. His research has focused on human microbiome

The human heart beats over 2 billion times during an average lifetime, driven by rhythmic depolarizations initiated by cardiac pacemaker cells within the sinoatrial node (SAN; Figure 1A). These electrical impulses are distributed throughout the heart via the cardiac conduction system (CCS), which synchronizes the excitation-contraction coupling of atrial and ventricular myocytes.1 Failure to generate

BACKGROUND:Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).METHODS:This study

The ECM (extracellular matrix) is a major component of the vascular microenvironment that modulates vascular homeostasis. ECM proteins include collagens, elastin, noncollagen glycoproteins, and proteoglycans/glycosaminoglycans. ECM proteins form complex matrix structures, such as the basal lamina and collagen and elastin fibers, through direct interactions or lysyl oxidase-mediated cross-linking. Moreover

RATIONALE:Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the early morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood.OBJECTIVE:The objectives are to investigate the recruitment of transcription factors to time-of-day differentially

BACKGROUND:In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3′,5′-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins)

Energetic demand and nutrient supply fluctuate as a function of time-of-day, in alignment with sleep-wake and fasting-feeding cycles. These daily rhythms are mirrored by 24-hour oscillations in numerous cardiovascular functional parameters, including blood pressure, heart rate, and myocardial contractility. It is, therefore, not surprising that metabolic processes also fluctuate over the course of

Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns

The impact of circadian rhythms on cardiovascular function and disease development is well established, with numerous studies in genetically modified animals emphasizing the circadian molecular clock’s significance in the pathogenesis and pathophysiology of myocardial ischemia and heart failure progression. However, translational preclinical studies targeting the heart's circadian biology are just

The brain is a complex organ, fundamentally changing across the day to perform basic functions like sleep, thought, and regulating whole-body physiology. This requires a complex symphony of nutrients, hormones, ions, neurotransmitters and more to be properly distributed across the brain to maintain homeostasis throughout 24 hours. These solutes are distributed both by the blood and by cerebrospinal

The blood-brain barrier (BBB) is a critical interface separating the central nervous system from the peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled a profound connection between the BBB and circadian rhythms, the endogenous oscillations synchronizing biological processes with the 24-hour light-dark cycle. This review explores the significance of circadian

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying

BACKGROUND:Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix

BACKGROUND:Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154

All living organisms on Earth demonstrate rhythms in biological function, which are approximately tied to the 24-hour cycle of a single day and night. The term diurnal is commonly used to describe events that occur during the day. For example, a diurnal species is the one that is mainly active during the daylight. In contrast, the term circadian refers to a rhythm that has a period of ≈24 hours but

The timing of life on Earth is remarkable: between individuals of the same species, a highly similar temporal pattern is observed, with shared periods of activity and inactivity each day. At the individual level, this means that over the course of a single day, a person alternates between two states. They are either upright, active, and communicative or they lie down in a state of (un)consciousness

Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular

Mammalian physiology and cellular function are subject to significant oscillations over the course of every 24-hour day. It is likely that these daily rhythms will affect function as well as mechanisms of disease in the central nervous system. In this review, we attempt to survey and synthesize emerging studies that investigate how circadian biology may influence the neurovascular unit. We examine

Circadian rhythms exert a profound impact on most aspects of mammalian physiology, including the immune and cardiovascular systems. Leukocytes engage in time-of-day–dependent interactions with the vasculature, facilitating the emigration to and the immune surveillance of tissues. This review provides an overview of circadian control of immune-vascular interactions in both the steady state and cardiovascular

Hypertension is extremely common, affecting approximately 1 in every 2 adults globally. Chronic hypertension is the leading modifiable risk factor for cardiovascular disease and premature mortality worldwide. Despite considerable efforts to define mechanisms that underlie hypertension, a potentially major component of the disease, the role of circadian biology has been relatively overlooked in both

BACKGROUND:Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change

BACKGROUND:CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms.METHODS:Plasma

BACKGROUND:While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions,

BACKGROUND:Systemic sclerosis (SSc) is a connective tissue disease that can serve as a model to study vascular changes in response to inflammation, autoimmunity, and fibrotic remodeling. Although microvascular changes are the earliest histopathologic manifestation of SSc, the vascular pathophysiology remains poorly understood.METHODS:We applied spatial proteomic approaches to deconvolute the heterogeneity

BACKGROUND:Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined.METHODS:High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral

The crosstalk of the heart with distant organs such as the lung, liver, gut, and kidney has been intensively approached lately. The kidney is involved in (1) the production of systemic relevant products, such as renin, as part of the most essential vasoregulatory system of the human body, and (2) in the clearance of metabolites with systemic and organ effects. Metabolic residue accumulation during

On June 10, 2024, the American Heart Association (AHA) enters its 100th year as an organization dedicated to the fight against heart disease and stroke, thus fostering a world of longer, healthier lives. This critical work includes essential lifesaving measures such as annual CPR training for ≈22 million people and enrolling more than 2600 hospitals in Get With The Guidelines, a program that provides

Ponatinib is used for the treatment of particular cases of chronic myeloid leukemia (CML) that don’t respond to other medications. Unfortunately, the drug can have life-threatening cardiovascular side effects including cardiomyopathy and heart failure. Ponatinib is known to induce mitochondrial dysfunction, which is linked to the cellular stress response. But whether the drug itself activates the stress