-
Cell Cycle (Georgetown, Tex.) Jul 2023This study aims to investigate how exercise-induced myocardial hypertrophy preconditioning affects cardiac fibroblasts in the context of myocardial fibrosis, a chronic...
This study aims to investigate how exercise-induced myocardial hypertrophy preconditioning affects cardiac fibroblasts in the context of myocardial fibrosis, a chronic disease that can cause cardiac arrhythmia and heart failure. Heart failure was induced in male C57BL/6 mice via Transverse aortic constriction, and some mice were given swimming exercise before surgery to test the effects of exercise-induced myocardial hypertrophy preconditioning on myocardial fibrosis. Myocardial tissue was evaluated for fibrosis, senescent cells, and apoptotic cells. Myocardial fibroblasts from rats were cultured and treated with norepinephrine to induce fibrosis which were then treated with si-Nrf2 and analyzed for markers of fibrosis, senescence, apoptosis, and cell proliferation. Exercise-induced myocardial hypertrophy preconditioning reduced myocardial fibrosis in mice, as shown by decreased mRNA expression levels of fibrosis-related indicators and increased cell senescence. In vitro data indicated that norepinephrine (NE) treatment increased fibrosis-related markers and reduced apoptotic and senescent cells, and this effect was reversed by pre-conditioning in PRE+NE group. Preconditioning activated Nrf2 and downstream signaling genes, promoting premature senescence in cardiac fibroblasts and tissues isolated from preconditioned mice. Moreover, Nrf2 knockdown reversed proapoptotic effects, restored cell proliferation, reduced senescence-related protein expression, and increased oxidative stress markers and fibrosis-related genes, indicating Nrf2's crucial role in regulating oxidative stress response of cardiac fibroblasts. Exercise-induced myocardial hypertrophy preconditioning improves myocardial fibrosis which is Nrf2-dependent, indicating the protective effect of hypertrophy preconditioning. These findings may contribute to the development of therapeutic interventions to prevent or treat myocardial fibrosis.
Topics: Male; Rats; Mice; Animals; NF-E2-Related Factor 2; Mice, Inbred C57BL; Myocardium; Cardiomyopathies; Heart Failure; Signal Transduction; Hypertrophy; Fibroblasts; Fibrosis; Norepinephrine
PubMed: 37312565
DOI: 10.1080/15384101.2023.2215081 -
Raman Spectroscopy and Microscopy Applications in Cardiovascular Diseases: From Molecules to Organs.Biosensors Nov 2018Noninvasive and label-free vibrational spectroscopy and microscopy methods have shown great potential for clinical diagnosis applications. Raman spectroscopy is based on... (Review)
Review
Noninvasive and label-free vibrational spectroscopy and microscopy methods have shown great potential for clinical diagnosis applications. Raman spectroscopy is based on inelastic light scattering due to rotational and vibrational modes of molecular bonds. It has been shown that Raman spectra provide chemical signatures of changes in biological tissues in different diseases, and this technique can be employed in label-free monitoring and clinical diagnosis of several diseases, including cardiovascular studies. However, there are very few literature reviews available to summarize the state of art and future applications of Raman spectroscopy in cardiovascular diseases, particularly cardiac hypertrophy. In addition to conventional clinical approaches such as electrocardiography (ECG), echocardiogram (cardiac ultrasound), positron emission tomography (PET), cardiac computed tomography (CT), and single photon emission computed tomography (SPECT), applications of vibrational spectroscopy and microscopy will provide invaluable information useful for the prevention, diagnosis, and treatment of cardiovascular diseases. Various in vivo and ex vivo investigations can potentially be performed using Raman imaging to study and distinguish pathological and physiological cardiac hypertrophies and understand the mechanisms of other cardiac diseases. Here, we have reviewed the recent literature on Raman spectroscopy to study cardiovascular diseases covering investigations on the molecular, cellular, tissue, and organ level.
Topics: Cardiomegaly; Cardiovascular Diseases; Positron-Emission Tomography; Spectrum Analysis, Raman; Tomography, Emission-Computed, Single-Photon
PubMed: 30424523
DOI: 10.3390/bios8040107 -
American Journal of Physiology. Heart... Sep 2017The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure... (Review)
Review
The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF. We discuss the significance of alterations in energy supply (substrate utilization, oxidative capacity, and phosphotransfer) and energy sensing using observations from human and animal disease models and models of manipulated energy supply/sensing. We aim to provide ways of thinking about metabolic remodeling that center around metabolic flexibility, capacity (reserve), and efficiency rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodeling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative, and phosphotransfer) represents a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts.
Topics: Adaptation, Physiological; Animals; Cardiomegaly; Disease Progression; Energy Metabolism; Heart Failure; Humans; Myocardium; Phenotype
PubMed: 28646030
DOI: 10.1152/ajpheart.00731.2016 -
Endokrynologia Polska 2020Not required for Clinical Vignette.
Not required for Clinical Vignette.
Topics: Breast; Child; Estrogen Antagonists; Female; Humans; Hypertrophy
PubMed: 31909454
DOI: 10.5603/EP.a2019.0063 -
Skeletal Muscle Jul 2022Skeletal muscle homeostasis and function are ensured by orchestrated cellular interactions among several types of cells. A noticeable aspect of skeletal muscle biology... (Review)
Review
Skeletal muscle homeostasis and function are ensured by orchestrated cellular interactions among several types of cells. A noticeable aspect of skeletal muscle biology is the drastic cell-cell communication changes that occur in multiple scenarios. The process of recovering from an injury, which is known as regeneration, has been relatively well investigated. However, the cellular interplay that occurs in response to mechanical loading, such as during resistance training, is poorly understood compared to regeneration. During muscle regeneration, muscle satellite cells (MuSCs) rebuild multinuclear myofibers through a stepwise process of proliferation, differentiation, fusion, and maturation, whereas during mechanical loading-dependent muscle hypertrophy, MuSCs do not undergo such stepwise processes (except in rare injuries) because the nuclei of MuSCs become directly incorporated into the mature myonuclei. In this review, six specific examples of such differences in MuSC dynamics between regeneration and hypertrophy processes are discussed.
Topics: Cell Differentiation; Humans; Hypertrophy; Muscle, Skeletal; Myoblasts; Regeneration
PubMed: 35794679
DOI: 10.1186/s13395-022-00300-0 -
Critical Reviews in Biochemistry and... 2014The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network... (Review)
Review
The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.
Topics: Animals; Cachexia; Humans; Hypertrophy; Muscle, Skeletal; Muscular Atrophy; Signal Transduction
PubMed: 24237131
DOI: 10.3109/10409238.2013.857291 -
Journal of Applied Physiology... Nov 2015Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is... (Review)
Review
Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca(2+) turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.
Topics: Animals; Calcium Signaling; Heart Failure; Humans; Hypertrophy, Left Ventricular; Myocardium; Stroke Volume
PubMed: 26183480
DOI: 10.1152/japplphysiol.00374.2015 -
Physiological Reports Apr 2022Mitochondria in the skeletal muscle are essential for maintaining metabolic plasticity and function. Mitochondrial quality control encompasses the dynamics of the...
Mitochondria in the skeletal muscle are essential for maintaining metabolic plasticity and function. Mitochondrial quality control encompasses the dynamics of the biogenesis and remodeling of mitochondria, characterized by the constant fission and fusion of mitochondria in response to metabolic stressors. However, the roles of mitochondrial fission or fusion in muscle hypertrophy and atrophy remain unclear. The aim of this study was to determine whether mitochondrial fusion and fission events are influenced by muscle hypertrophy or atrophy stimulation. Twenty-six male F344 rats were randomly assigned to a control group or were subjected to up to 14 days of either plantaris overload (via tenotomy of the gastrocnemius and soleus muscles; hypertrophy group) or hindlimb cast immobilization (atrophy group). After 14 days of treatment, plantaris muscle samples were collected to determine the expression levels of mitochondrial fusion- and fission-related proteins. Muscle weight and total muscle protein content increased following plantaris overload in the hypertrophy group, but decreased following immobilization for 14 days in the atrophy group. In the hypertrophied muscle, the level of activated dynamin-related protein 1 (Drp1), phosphorylated at Ser616, significantly increased by 25.8% (p = 0.014). Moreover, the protein expression level of mitochondrial fission factor significantly decreased by 36.5% in the hypertrophy group compared with that of the control group (p = 0.017). In contrast, total Drp1 level significantly decreased in the atrophied plantaris muscle (p = 0.011). Our data suggest that mitochondrial fission events may be influenced by both muscle hypertrophy and atrophy stimulation, and that mitochondrial fission- related protein Drp1 plays an important role in the regulation of skeletal muscle in response to mechanical stimulation.
Topics: Animals; Atrophy; Hypertrophy; Male; Mitochondrial Dynamics; Mitochondrial Proteins; Muscle, Skeletal; Rats; Rats, Inbred F344
PubMed: 35439362
DOI: 10.14814/phy2.15281 -
Trends in Cardiovascular Medicine Nov 2011In response to injury, the myocardium hypertrophies in an attempt to maintain or augment function, which is associated with ventricular remodeling and changes in... (Review)
Review
In response to injury, the myocardium hypertrophies in an attempt to maintain or augment function, which is associated with ventricular remodeling and changes in capillary density. During the compensatory phase of the hypertrophic response, the myocardium maintains output and is characterized by a coordinated neo-angiogenic and fibrotic response that supports cardiomyocyte health and survival. Emerging evidence shows that paracrine-mediated cross talk between cardiac myocytes and nonmyocytes within the heart is critical for cardiac adaptation to stress, including the extent of hypertrophy and angiogenesis. This review discusses recent results indicating that placental growth factor (PGF; also called PlGF), a secreted factor within the vascular endothelial growth factor superfamily, is a pivotal mediator of adaptive cardiac hypertrophy and beneficial angiogenesis through its ability to coordinate the intercellular communication between different cell types in the heart.
Topics: Adaptation, Physiological; Animals; Cardiomegaly; Humans; Myocardium; Neovascularization, Physiologic; Paracrine Communication; Placenta Growth Factor; Pregnancy Proteins; Signal Transduction; Ventricular Remodeling
PubMed: 22902069
DOI: 10.1016/j.tcm.2012.05.014 -
Journal of Applied Physiology... Oct 2020Skeletal disuse can cause an accumulation of bone marrow adipose tissue (MAT) characterized by a combination of marrow adipocyte hyperplasia and/or hypertrophy. The...
Skeletal disuse can cause an accumulation of bone marrow adipose tissue (MAT) characterized by a combination of marrow adipocyte hyperplasia and/or hypertrophy. The malleability of MAT accumulation and of the hyperplasia and hypertrophy upon remobilization is unknown. In this study, we showed extensive hyperplasia and accelerated hypertrophy of bone marrow adipocytes in the proximal tibia epiphysis of rat knees immobilized for durations between 1 and 32 wk. Similar histomorphometric measures of adipocytes carried out in unoperated controls allowed distinguishing the effects of immobilization from the effects of aging. Although both knee immobilization and aging led to adipocyte hypertrophy, adipocyte hyperplasia was the hallmark signature effect of immobilization on MAT. Both bone marrow adipocyte hyperplasia and hypertrophy were sustained despite knee remobilization for durations up to four times the duration of immobilization. These results suggest that adipocyte hyperplasia is the predominant mechanism explaining MAT accumulation in skeletal disuse. In this model, the changes were unremitting for the investigated time points. Investigating the cellular and molecular mechanisms of marrow adipocyte mechanoregulation will be important to better understand how adipocytes adapt to changes in mechanical environments. This longitudinal study elucidates the response of marrow adipose tissue adipocytes in weight-bearing joints to changes in different mechanical environments, and we provide insight on the malleability of the changes over time. In a rat animal model, knee immobilization induced hyperplasia and accelerated the age-dependent hypertrophy of adipocytes. Changes in adipocyte number and size were sustained despite unassisted remobilization. Multimodal distributions of cell size were characteristic of bone marrow adipocytes.
Topics: Adipocytes; Animals; Bone Marrow; Hyperplasia; Hypertrophy; Longitudinal Studies; Rats
PubMed: 32853104
DOI: 10.1152/japplphysiol.00539.2020