-
Frontiers in Endocrinology 2023Fibroblast growth factor (FGF)23 is a bone-derived phosphotropic hormone that regulates phosphate and mineral homeostasis. Recent studies have provided evidence that a... (Review)
Review
Fibroblast growth factor (FGF)23 is a bone-derived phosphotropic hormone that regulates phosphate and mineral homeostasis. Recent studies have provided evidence that a high plasma concentration of FGF23 is associated with cardiac disease, including left ventricular hypertrophy (LVH), heart failure, atrial fibrillation, and cardiac death. Experimental studies have shown that FGF23 activates fibroblast growth factor receptor 4 (FGFR4)/phospholipase Cγ/calcineurin/nuclear factor of activated T-cells signaling in cardiomyocytes and induces cardiac hypertrophy in rodents. Activation of FGFR4 by FGF23 normally requires the co-receptor α-klotho, and klotho-independent signaling occurs only under conditions characterized by extremely high FGF23 concentrations. Recent studies have demonstrated that FGF23 activates the renin-angiotensin-aldosterone system (RAAS) and induces LVH, at least in part as a result of lower vitamin D activation. Moreover, crosstalk between FGF23 and RAAS results in the induction of cardiac hypertrophy and fibrosis. In this review, we summarize the results of studies regarding the relationships between FGF23 and cardiac events, and describe the potential direct and indirect mechanisms whereby FGF23 induces LVH.
Topics: Humans; Cardiomegaly; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Hypertrophy, Left Ventricular; Myocytes, Cardiac
PubMed: 36909314
DOI: 10.3389/fendo.2023.1059179 -
American Journal of Physiology. Heart... May 2022
Topics: Cardiomegaly; Humans; Myocytes, Cardiac
PubMed: 35394856
DOI: 10.1152/ajpheart.00162.2022 -
Current Hypertension Reports May 2021Resistant hypertension (RH) is a major contributor to cardiovascular diseases and is associated with increased all-cause and cardiovascular mortality. Cardiac changes... (Review)
Review
PURPOSE OF REVIEW
Resistant hypertension (RH) is a major contributor to cardiovascular diseases and is associated with increased all-cause and cardiovascular mortality. Cardiac changes such as impaired left ventricular (LV) function, left ventricular hypertrophy (LVH), myocardial fibrosis, and enlarged left atrium (LA) are consequences of chronic exposure to an elevated blood pressure. The purpose of this review article is to demonstrate the potential benefits of using STE as a non-invasive imaging technique in the assessment of cardiac remodeling in patients with hypertension and specifically in uncontrolled and RH population.
RECENT FINDINGS
It is well-recognized that conventional transthoracic echocardiography is a useful analytic imaging modality to evaluate hypertension-mediated organ damage (HMOD) and in a resistant hypertensive population. More recently two-dimensional speckle tracking echocardiography (STE) has been utilized to provide further risk assessment to this population. Recent data has shown that STE is a new promising echocardiographic marker to evaluate early stage LV dysfunction and myocardial fibrosis over conventional 2D parameters in patients with cardiovascular diseases.
Topics: Echocardiography; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardium; Ventricular Dysfunction, Left
PubMed: 33950321
DOI: 10.1007/s11906-021-01148-3 -
Nature Communications Jan 2022Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental...
Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome. Here we report genome-wide analysis of mRNA methyladenosine (mA) dynamics of skeletal muscle hypertrophic growth following overload-induced stress. We show that increases in METTL3 (the mA enzyme), and concomitantly mA, control skeletal muscle size during hypertrophy; exogenous delivery of METTL3 induces skeletal muscle growth, even without external triggers. We also show that METTL3 represses activin type 2 A receptors (ACVR2A) synthesis, blunting activation of anti-hypertrophic signaling. Notably, myofiber-specific conditional genetic deletion of METTL3 caused spontaneous muscle wasting over time and abrogated overload-induced hypertrophy; a phenotype reverted by co-administration of a myostatin inhibitor. These studies identify a previously unrecognized post-transcriptional mechanism promoting the hypertrophic response of skeletal muscle via control of myostatin signaling.
Topics: Activin Receptors, Type II; Adenosine; Animals; Dependovirus; Gene Expression Regulation, Developmental; Genetic Vectors; Genome-Wide Association Study; Hypertrophy; Male; Methyltransferases; Mice; Muscle Development; Muscle, Skeletal; Muscular Atrophy; Myostatin; Signal Transduction
PubMed: 35013323
DOI: 10.1038/s41467-021-27848-7 -
Physiological Reports Aug 2023Stanniocalcin-2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the...
AIMS
Stanniocalcin-2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the metalloproteinase PAPP-A, which promotes muscle growth by upregulating the insulin-like growth factor (IGF) axis. The aim was to examine if STC2 affects skeletal muscle mass and to assess how the IGF axis mediates muscle hypertrophy induced by functional overload.
METHODS
We compared muscle mass and muscle fiber morphology between Stc2 (n = 21) and wild-type (n = 15) mice. We then quantified IGF1, IGF2, IGF binding proteins -4 and -5 (IGFBP-4, IGFBP-5), PAPP-A and STC2 in plantaris muscles of wild-type mice subjected to 4-week unilateral overload (n = 14).
RESULTS
Stc2 mice showed up to 10% larger muscle mass compared with wild-type mice. This increase was mediated by greater cross-sectional area of muscle fibers. Overload increased plantaris mass and components of the IGF axis, including quantities of IGF1 (by 2.41-fold, p = 0.0117), IGF2 (1.70-fold, p = 0.0461), IGFBP-4 (1.48-fold, p = 0.0268), PAPP-A (1.30-fold, p = 0.0154) and STC2 (1.28-fold, p = 0.019).
CONCLUSION
Here we provide evidence that STC2 is an inhibitor of muscle growth upregulated, along with other components of the IGF axis, during overload-induced muscle hypertrophy.
Topics: Animals; Mice; Glycoproteins; Hypertrophy; Insulin-Like Growth Factor Binding Protein 4; Insulin-Like Growth Factor I; Muscle, Skeletal; Peptide Hormones; Pregnancy-Associated Plasma Protein-A
PubMed: 37568262
DOI: 10.14814/phy2.15793 -
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 -
International Journal of Molecular... Aug 2023Injury to skeletal muscle through trauma, physical activity, or disease initiates a process called muscle regeneration. When injured myofibers undergo necrosis, muscle... (Review)
Review
Injury to skeletal muscle through trauma, physical activity, or disease initiates a process called muscle regeneration. When injured myofibers undergo necrosis, muscle regeneration gives rise to myofibers that have myonuclei in a central position, which contrasts the normal, peripheral position of myonuclei. Myofibers with central myonuclei are called regenerating myofibers and are the hallmark feature of muscle regeneration. An important and underappreciated aspect of muscle regeneration is the maturation of regenerating myofibers into a normal sized myofiber with peripheral myonuclei. Strikingly, very little is known about processes that govern regenerating myofiber maturation after muscle injury. As knowledge of myofiber formation and maturation during embryonic, fetal, and postnatal development has served as a foundation for understanding muscle regeneration, this narrative review discusses similarities and differences in myofiber maturation during muscle development and regeneration. Specifically, we compare and contrast myonuclear positioning, myonuclear accretion, myofiber hypertrophy, and myofiber morphology during muscle development and regeneration. We also discuss regenerating myofibers in the context of different types of myofiber necrosis (complete and segmental) after muscle trauma and injurious contractions. The overall goal of the review is to provide a framework for identifying cellular and molecular processes of myofiber maturation that are unique to muscle regeneration.
Topics: Humans; Muscle, Skeletal; Exercise; Hypertrophy; Muscle Development; Necrosis
PubMed: 37628725
DOI: 10.3390/ijms241612545 -
Biomedicine & Pharmacotherapy =... Jan 2024The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast...
The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis.
Topics: Rats; Mice; Animals; Cardiomegaly; Myocardium; Myocytes, Cardiac; Fibrosis; Mice, Inbred C57BL; Angiotensin II; Ventricular Remodeling
PubMed: 38091641
DOI: 10.1016/j.biopha.2023.116002 -
Virchows Archiv : An International... Jul 2021Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the...
Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the heart weight, size, and thickness as well as a systematic use of cut off values for normality by age, gender, and body weight and height are needed. For these reasons, recommendations have been written on behalf of the Association for European Cardiovascular Pathology. The diagnostic work up implies the search for pressure and volume overload conditions, compensatory hypertrophy, storage and infiltrative disorders, and cardiomyopathies. Although some gross morphologic features can point to a specific diagnosis, systematic histologic analysis, followed by possible immunostaining and transmission electron microscopy, is essential for a final diagnosis. If the autopsy is carried out in a general or forensic pathology service without expertise in cardiovascular pathology, the entire heart (or pictures) together with mapped histologic slides should be sent for a second opinion to a pathologist with such an expertise. Indication for postmortem genetic testing should be integrated into the multidisciplinary management of sudden cardiac death.
Topics: Autopsy; Cardiomegaly; Cause of Death; Genetic Testing; Humans; Myocardium; Organ Size; Predictive Value of Tests; Risk Factors; Terminology as Topic
PubMed: 33740097
DOI: 10.1007/s00428-021-03038-0 -
Cold Spring Harbor Perspectives in... Mar 2020Within the realm of zoological study, the question of how an organism reaches a specific size has been largely unexplored. Recently, studies performed to understand the... (Review)
Review
Within the realm of zoological study, the question of how an organism reaches a specific size has been largely unexplored. Recently, studies performed to understand the regulation of organ size have revealed that both cellular signals and external cues contribute toward the determination of total cell mass within each organ. The establishment of final organ size requires the precise coordination of cell growth, proliferation, and survival throughout development and postnatal life. In the mammalian heart, the regulation of size is biphasic. During development, cardiomyocyte proliferation predominantly determines cardiac growth, whereas in the adult heart, total cell mass is governed by signals that regulate cardiac hypertrophy. Here, we review the current state of knowledge regarding the extrinsic factors and intrinsic mechanisms that control heart size during development. We also discuss the metabolic switch that occurs in the heart after birth and precedes homeostatic control of postnatal heart size.
Topics: Animals; Cardiomegaly; Cell Cycle; Cell Proliferation; Cell Survival; Heart; Humans; Hypertrophy; Myocardium; Myocytes, Cardiac; Organ Size; Organogenesis; Signal Transduction; Somatomedins; Zoology
PubMed: 31615785
DOI: 10.1101/cshperspect.a037150