American Journal of Physiology. Heart and Circulatory Physiology

Endothelial cells (ECs) within the vascular system encounter fluid shear stress (FSS). High, laminar FSS promotes vasodilation and anti-inflammatory responses, while low or disturbed FSS induces dysfunction and inflammation. However, the adaptation of ECs to dynamically changing FSS patterns remains underexplored. Here, by combining traction force microscopy with a custom flow chamber, we examined human umbilical vein endothelial cells adapting their traction during transitions from short-term low shear to long-term high shear stress...

Increased left atrial (LA) size and reduced LA function have been associated with heart failure and atrial fibrillation (AF) in at risk populations. However, atrial remodeling has also been associated with exercise training and the relationship between fitness, LA size and function has not been defined across the fitness spectrum. In a cross-sectional study of 559 ostensibly healthy participants, comprising 304 males (mean age 46 ± 20 years) and 255 females (mean age 47 ± 15 years), we sought to define the relationship between cardiorespiratory fitness (CRF), LA size and function...

A significant number of pregnancies occur at advanced maternal age (>35 years), which is a risk factor for pregnancy complications. Healthy pregnancies require massive hemodynamic adaptations, including an increased blood volume and cardiac output. There is growing evidence that these cardiovascular adaptations are impaired with age, however, little is known about maternal cardiac function with advanced age. We hypothesized that cardiac adaptations to pregnancy are impaired with advanced maternal age. Younger (4 months; ~early reproductive maturity in humans) and aged (9 months; ~35 years in humans) pregnant Sprague-Dawley rats were assessed and compared to age-matched non-pregnant controls...

Daylight saving time (DST) is a Western biannual time transition, setting the clock back one hour in the fall and forward one hour in the spring. There is an epidemiological link between DST and acute myocardial infarction risk in the first week following the spring shift; however, the mechanisms underlying the effect of DST on cardiovascular function remain unclear. The purpose of this study was to explore the short-term cardiovascular changes induced by fall and spring shifts in DST in a convenience sample of healthy adults...

Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding mechanisms preventing or exacerbating disease progression. Literature suggests an important role for activation of interleukin 13 or interleukin 4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans...

Atherosclerotic cardiovascular disease is a chronic condition that often co-presents with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetics endorsed by major professional societies for improving glycemic status and reducing atherosclerotic risk in people living with type 2 diabetes. While the cardioprotective efficacy of GLP-1RAs and their relationship with traditional risk factors are well-established, there is a paucity of publications that have summarized the potentially direct mechanisms through which GLP-1RAs mitigate atherosclerosis...

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI) were calculated before, during, and after 20955 desaturations from lead II electrocardiography signals of 492 suspected OSA patients (52% men)...

Biological sex is a salient factor in exercise-induced vascular adaptation. While a male bias is apparent in the literature, the methodological quality of available studies in females is not yet known. This systematic review with narrative synthesis aimed to assess available evidence of exercise interventions on endothelial function, measured using flow-mediated dilation, in otherwise healthy individuals and athletes. A standardized audit framework was applied to quantify the representation of female participants...

Background - Recently, a method to estimate wedge pressure (Pw) corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw-measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw-measurements and the derivation of Pw-corrected MR...

Athlete's heart is generally regarded as a physiological adaptation to regular training, with specific morphological and functional alterations in the cardiovascular system. Development of the non-invasive imaging techniques over the last several years enabled better assessment of cardiac remodeling in athletes, which may eventually mimic certain pathological conditions with the potential for sudden cardiac death, or disease progression. The current literature provides a compelling overview of the available methods that target the interrelation of prolonged exercise with cardiac structure and function...

Whether cerebral sympathetic-mediated vasomotor control can be modulated by local brain activity remains unknown. This study tested the hypothesis that application or removal of a cognitive task during a cold pressor test (CPT) would attenuate and restore decreases in cerebrovascular conductance (CVC), respectively. Middle cerebral artery blood velocity (transcranial Doppler) and mean arterial pressure (finger photoplethysmography) were examined in healthy adults (n=16; 8 F and 8 M) who completed a control CPT, followed by a CPT coupled with a cognitive task administered either A) 30 s after the onset of the CPT and for the duration of the CPT or B) at the onset of the CPT and terminated 30 s prior to the end of the CPT (condition order was counterbalanced)...

Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown to provide beneficial clinical outcomes for HFpEF patients. Using a two-hit HFpEF murine model, we studied cardiac reverse remodelling (RR) after stopping the causing stress and introducing voluntary exercise (VE). We checked in 2-month-old male and female C57Bl6/J mice the heart's response to angiotensin II (AngII; 1...

BACKGROUND: The magnitude of exercise-induced cardiac troponin (cTn) elevations is dependent on cardiovascular health status, and previous studies have shown that occult coronary atherosclerosis is highly prevalent among amateur athletes. We tested the hypothesis that middle-aged and older athletes with coronary atherosclerosis demonstrate greater cTn elevations following a controlled endurance exercise test compared to healthy peers. METHODS: We included 59 male athletes from the MARC-2 study and stratified them as controls (coronary artery calcium score (CACS) = 0, n=20), high CACS (≥300 Agatston Units or ≥75th MESA percentile, n=20) or significant stenosis (≥50% in any coronary artery, n=19)...

Sex-based differences in the development of obesity-induced cardio-metabolic dysfunction are well documented, however the specific mechanisms are not completely understood. Obesity has been linked to dysregulation of the epitranscriptome, but the role of N6-methyladenosine (m6A) RNA methylation has not been investigated in relation to the sex differences during obesity-induced cardiac dysfunction. In the current study, male and female C57BL/6J mice were subjected to short- and long-term high-fat/high-sucrose (HFHS) diet to induce obesogenic stress...

Sustained hemodynamic pressure-overload(PO) produced by murine transverse aortic constriction(TAC) causes myocardial fibrosis; removal of TAC(unTAC) returns LV hemodynamic load to normal and results in significant, but incomplete regression of myocardial fibrosis. However, the cellular mechanisms that result in these outcomes have not been defined. The objective was to determine temporal changes in myocardial macrophage phenotype in TAC and unTAC and determine whether macrophage depletion alters collagen degradation after unTAC...

CONTEXT: Imaging tools are crucial for studying the vascular network and its barrier function in various physiopathological conditions. Shortwave infrared window (SWIR) optical imaging allows non-invasive, in-depth exploration. We applied SWIR imaging, combined with vessel segmentation and deep learning analyses, to study real-time dextran probe extravasation in mice experiencing intermittent hypoxia-a characteristic of obstructive sleep apnea associated with potential cardiovascular alterations due to early vascular permeability...

The arterial system is integral to the proper function of all other organs and tissues. Arterial function is impaired with aging, and arterial dysfunction contributes to the development of numerous age-related diseases, including cardiovascular diseases. The gut microbiome has emerged as an important regulator of both normal host physiological function and impairments in function with aging. The purpose of this review is to summarize more recently published literature demonstrating the role of the gut microbiome in supporting normal arterial development and function and in modulating arterial dysfunction with aging in the absence of overt disease...

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 weeks of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the <u>R</u>educed <u>U</u>terine <u>P</u>erfusion <u>P</u>ressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology...

Exercise testing unmasks more exaggerated systolic blood pressure responses (SBP) in Black compared to White male adults. Such responses, if translatable to females, may detect racial disparities particularly relevant during menopause. Given the endothelial involvement in BP regulation and as a source of fibrinolytic markers, it follows that fibrinolytic and BP response to exercise could be linked. Thus, we examined BP and fibrinolytic responses to exercise testing in Black and White postmenopausal females...

Few training studies have assessed the impact of different modes of exercise on changes in cardiac function. This study investigated changes in left ventricular (LV) systolic and diastolic function following endurance (END) and resistance (RES) training in healthy participants. 64 individuals participated in a randomized cross-over design trial, involving 12-weeks of END and RES training, separated by a 12-week washout. Echocardiograms assessed systolic function (ejection fraction (EF), and global longitudinal strain (GLS)), diastolic function (mitral valve early velocity (E), tissue Doppler velocity (e'), their ratio (E/e')), and left atrial volume indexed to body surface area (LA ESVi)...