American Journal of Physiology. Heart and Circulatory Physiology

Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated in the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na+ current (INaL ) in cardiomyocytes, raising the possibility that INaL conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain-of-function, GoF) or ablated (loss-of-function, LoF) mutations of the sodium channel Nav1...

BACKGROUND: It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin Lymphoma (HL) survivors. We test the hypothesis that: 1) MBF response during mental stress (MS) is impaired in long-term HL survivors; 2) Aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. METHODS: Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: Exercise-trained (HLT, n=10) and untrained (HLUT, n=10)...

Cardiovascular disease (CVD) and cancer are the leading causes of mortality worldwide. Although generally thought of as distinct diseases, the intersectional overlap between CVD and cancer is increasingly evident in both causal and mechanistic relationships. The field of cardio-oncology is largely focused on cardiotoxic effects of cancer therapies (e.g., chemotherapy, radiation). Further, the cumulative effects of cardiotoxic therapy exposure and the prevalence of CVD risk factors in cancer patients leads to long-term morbidity and poor quality of life in this patient population-even when patients are cancer-free...

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common cause of pulmonary hypertension (PH) worldwide and is strongly associated with adverse clinical outcomes. The American Heart Association recently highlighted a call to action regarding the distinct lack of evidence-based treatments for PH due to poorly understood pathophysiology of PH attributable to HFpEF (PH-HFpEF). Prior studies have described cardio-physiological mechanisms to explain the development of isolated postcapillary PH (ipc-PH); however, the consequent increased pulmonary vascular (PV) resistance (PVR) may lead to the less understood and more fatal combined pre- and postcapillary PH (cpc-PH)...

Cardiovascular research relies heavily on the veracity of in vitro cardiomyocyte models, with HL-1 and H9c2 cell lines at the forefront due to their cardiomyocyte-like properties. However, the variability stemming from non-standardized culturing and transfection methods poses a significant challenge to data uniformity and reliability. In this study, we introduce meticulously crafted protocols to enhance the culture and transfection of HL-1 and H9c2 cells, emphasizing the reduction of cytotoxic effects while improving transfection efficiency...

We aim to examine the association of sleep duration, sleep quality, late chronotype and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ)...

Cardiac hypertrophy is a common feature in several cardiomyopathies. We previously reported that loss of ADAM15 (disintegrin and metalloproteinase 15) worsened cardiac hypertrophy and dilated cardiomyopathy following cardiac pressure overload. Here, we investigated the impact of ADAM15 loss in female mice following cardiac pressure overload induced by transverse aortic constriction (TAC). Female Adam15-/- mice developed the same degree of cardiac hypertrophy, dilation and dysfunction as the parallel female wildtype (WT) mice at 6 weeks post-TAC...

Deterioration of physiological systems, like the cardiovascular system, occurs progressively with age impacting an individual's health and increasing susceptibility to injury and disease. Cellular senescence has an underlying role in age-related alterations and can be triggered by natural aging or prematurely by stressors such as the bacterial toxin, lipopolysaccharide (LPS). The metabolism of polyunsaturated fatty acids (PUFAs) by CYP450 enzymes produces numerous bioactive lipid mediators that can be further metabolized by soluble epoxide hydrolase (sEH) into diol metabolites, often with reduced biological effects...

INTRODUCTION: Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and non-binary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. METHODS: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET...

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases...

BACKGROUND: Clinical failure of arteriovenous fistulae (AVF) is frequently due to juxta-anastomotic neointimal hyperplasia (JANIH). Although the mouse AVF model recapitulates human AVF maturation, previous studies focused on the outflow vein distal to the anastomosis. We hypothesized that the juxta-anastomotic area (JAA) has increased NIH compared to the outflow vein. METHOD: AVF were created in C57BL/6 mice without or with chronic kidney disease (CKD). Temporal and spatial changes of the JAA were examined using histology and immunofluorescence...

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The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-week-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: non-pregnant (NP), mid-pregnancy (MP), late-pregnancy (LP), and 1-week post-birth (PB). Similar to our previous studies, we observed increased heart size during all stages of pregnancy (e.g., MP and LP) and post-birth (e...

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Premature ventricular complexes (PVCs) are spontaneous excitations occurring in the ventricles of the heart, which are associated with ventricular arrhythmias and sudden cardiac death. Under long QT conditions, PVCs can be mediated by repolarization gradient (RG) and early afterdepolarizations (EADs), yet the effects of heterogeneities or geometry of the RG or EAD regions on PVC genesis remain incompletely understood. In this study, we use computer simulation to systematically investigate the effects of the curvature of the RG border region on PVC genesis under long QT conditions...

Nicotine is the primary addictive component in tobacco products. Through its actions on the heart and autonomic nervous system, nicotine exposure is associated with electrophysiological changes and increased arrhythmia susceptibility. To assess underlying mechanisms, we treated rabbits with transdermal nicotine (NIC, 21 mg/day) or control (CT) patches for 28 days prior to performing dual optical mapping of transmembrane potential (RH237) and intracellular Ca2+ (Rhod-2 AM) in isolated hearts with intact sympathetic innervation...

Perivascular adipose tissue (PVAT) is increasingly recognized for its function in mechanotransduction. However, major gaps remain in our understanding of the cells present in PVAT, as well as how different cells contribute to mechanotransduction. We hypothesized that snRNA seq would reveal expression of mechanotransducers, and test one (PIEZO1) to illustrate the expression and functional agreement between single-nuclei RNA sequencing (snRNAseq) and physiological measurements. To contrast two brown tissues, subscapular brown adipose tissue (BAT) was also examined...

Increasing evidence indicates the role of mitochondrial and vascular dysfunction in aging and aging-associated pathologies; however, the exact mechanisms and chronological processes remain enigmatic. High energy demand organs, such as the brain, depend on the health of their mitochondria and vasculature in the maintenance of normal functions, therefore representing vulnerable targets for aging. This methodology paper describes an analysis pipeline for 3D mitochondria-associated signal geometry of two-photon image stacks of brain vasculature...

Peripheral artery disease (PAD) is a common vascular disease that primarily affects the lower limbs and is defined by the constriction or blockage of peripheral arteries and may involve microvascular dysfunction and tissue injury. Patients with diabetes have more prominent disease of microcirculation and develop peripheral neuropathy, autonomic dysfunction, and medial vascular calcification. Early and accurate diagnosis of PAD and disease characterization are essential for personalized management and therapy planning...

No abstract text is available yet for this article.