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Journal of Cellular and Molecular... Jun 2024Cardiac hypertrophy, worldwide known as an adaptive functional compensatory state of myocardial stress, is mainly believed to proceed to severe heart diseases, even to...
Cardiac hypertrophy, worldwide known as an adaptive functional compensatory state of myocardial stress, is mainly believed to proceed to severe heart diseases, even to sudden death. Emerging studies have explored the microRNA alteration during hypertrophy. However, the mechanisms of microRNAs involved in cardiac hypertrophy are still uncertain. We studied young rats to establish abdominal aorta coarctation (AAC) for 4 weeks. With the significant downregulated cardiac function and upregulated hypertrophic biomarkers, AAC-induced rats showed enlarged myocardiocytes and alterations in microRNAs, especially downregulated miR-31-5p. miR-31-5p targets the 3'UTR of Nfatc2ip and inhibits myocardial hypertrophy in vitro and in vivo. Furthermore, we verified that Nfatc2ip is necessary and sufficient for cardiac hypertrophy in neonatal rat cardiomyocytes. Moreover, we found miR-31-5p inhibited the colocalization of Nfatc2ip and hypertrophic gene β-Mhc. Luciferase assay and ChiP-qPCR test demonstrated that Nfatc2ip binded to the core-promoter of β-Mhc and enhanced its transcriptional activity. Above all, our study found a new pathway, mir-31-5p/Nfatc2ip/β-Mhc, which is involved in cardiac hypertrophy, suggesting a potential target for intervention of cardiac hypertrophy.
Topics: MicroRNAs; Animals; Cardiomegaly; NFATC Transcription Factors; Myocytes, Cardiac; Rats; Male; Rats, Sprague-Dawley; Gene Expression Regulation; 3' Untranslated Regions; Disease Models, Animal
PubMed: 38894694
DOI: 10.1111/jcmm.18413 -
International Journal of Molecular... Jun 2024Increased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during...
Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?
Increased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during pulmonary hypertension (PH). ROS molecules are produced in different compartments within the cell, with mitochondria known to produce the strongest ROS signal. Among ROS-forming mitochondrial proteins, outer-mitochondrial-membrane-located monoamine oxidases (MAOs, type A or B) are capable of degrading neurotransmitters, thereby producing large amounts of ROS. In mice, MAO-B is the dominant isoform, which is present in almost all cell types within the heart. We analyzed the effect of an inducible cardiomyocyte-specific knockout of MAO-B (cmMAO-B KO) for the development of RVH and RVF in mice. Right ventricular hypertrophy was induced by pulmonary artery banding (PAB). RV dimensions and function were measured through echocardiography. ROS production (dihydroethidium staining), protein kinase activity (PamStation device), and systemic hemodynamics (in vivo catheterization) were assessed. A significant decrease in ROS formation was measured in cmMAO-B KO mice during PAB compared to Cre-negative littermates, which was associated with reduced activity of protein kinases involved in hypertrophic growth. In contrast to littermates in which the RV was dilated and hypertrophied following PAB, RV dimensions were unaffected in response to PAB in cmMAO-B KO mice, and no decline in RV systolic function otherwise seen in littermates during PAB was measured in cmMAO-B KO mice. In conclusion, cmMAO-B KO mice are protected against RV dilatation, hypertrophy, and dysfunction following RV pressure overload compared to littermates. These results support the hypothesis that cmMAO-B is a key player in causing RV hypertrophy and failure during PH.
Topics: Animals; Hypertrophy, Right Ventricular; Monoamine Oxidase; Hypertension, Pulmonary; Mice; Mice, Knockout; Reactive Oxygen Species; Myocytes, Cardiac; Heart Failure; Male; Disease Models, Animal; Heart Ventricles; Ventricular Dysfunction, Right
PubMed: 38892401
DOI: 10.3390/ijms25116212 -
International Journal of Molecular... May 2024The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D...
Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice.
The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D signaling in the development of left ventricular (LV) hypertrophy and dysfunction. To ablate the vitamin D receptor (VDR) specifically in cardiomyocytes, VDR mice were crossed with Mlcv2-Cre mice. To induce LV hypertrophy experimentally by increasing cardiac afterload, transverse aortic constriction (TAC) was employed. Sham or TAC surgery was performed in 4-month-old, male, wild-type, VDR, Mlcv2-Cre, and cardiomyocyte-specific VDR knockout (VDR) mice. As expected, TAC induced profound LV hypertrophy and dysfunction, evidenced by echocardiography, aortic and cardiac catheterization, cardiac histology, and LV expression profiling 4 weeks post-surgery. Sham-operated mice showed no differences between genotypes. However, TAC VDR mice, while having comparable cardiomyocyte size and LV fibrosis to TAC VDR controls, exhibited reduced fractional shortening and ejection fraction as measured by echocardiography. Spatial transcriptomics of heart cryosections revealed more pronounced pro-inflammatory and pro-fibrotic gene regulatory networks in the stressed cardiac tissue niches of TAC VDR compared to VDR mice. Hence, our study supports the notion that vitamin D signaling in cardiomyocytes plays a protective role in the stressed heart.
Topics: Animals; Myocytes, Cardiac; Mice; Hypertrophy, Left Ventricular; Receptors, Calcitriol; Vitamin D; Gene Regulatory Networks; Fibrosis; Signal Transduction; Male; Disease Models, Animal; Mice, Knockout; Inflammation
PubMed: 38892126
DOI: 10.3390/ijms25115929 -
Aesthetic Plastic Surgery Jun 2024To investigate the postoperative effect of double-lid blepharoplasty based on the histological difference in the upper eyelid of Asian patients.
OBJECTIVE
To investigate the postoperative effect of double-lid blepharoplasty based on the histological difference in the upper eyelid of Asian patients.
MATERIAL AND METHODS
A total of 76 patients with poor bilateral upper eyelid morphology or a single eyelid were included in this study. Different techniques of double-eyelid blepharoplasty were performed based on the thickness of the palpebral tissue. The improved PARK method (group A: 15 participants) was employed for patients with orbicularis oculi muscle being thinner, and the fat bulge of orbital septum was less. The improved traditional method (group B: 52 participants) was employed for patients with hypertrophy of the eyelid skin, orbicularis oculi muscle, and fat bulge in the orbital septum.
RESULTS
All 76 patients achieved satisfactory outcomes in a single surgical procedure. Postoperative follow-up ranged from 3 to 6 months. In group A, there was no obvious swelling of flap near the palpebral margin and the double blepharon line becomes shallow. Although some patients in group B experienced varying degrees of bruising in the early postoperative period, all patients returned to a more natural shape 1-3 months after surgery. Furthermore, after 3-6 months postoperatively, there were no obvious scar adhesion and ladder sensation in the both sides of the incision.
CONCLUSION
Preoperative analysis of the thickness of the upper eyelid tissue is essential to determine the appropriate surgical technique for double-eyelid blepharoplasty. The improved traditional method is recommended for patients with hypertrophy of the upper eyelid tissue (group A), as it minimizes scar adhesion and reduces the stair-step sensation in the lower eyelid tissue during long-term follow-up. For patients with thin upper eyelid tissue, the improved PARK method should be employed to avoid issues such as tissue accumulation, double eyelid crease became shallower, or disappearance. In order to obtain natural and long-term surgical results, different surgical methods should be provided according to the patient's eye tissue condition.
LEVEL OF EVIDENCE II
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PubMed: 38890159
DOI: 10.1007/s00266-024-04051-9 -
Revue Neurologique Jun 2024
PubMed: 38890053
DOI: 10.1016/j.neurol.2024.06.001 -
The Journal of Sports Medicine and... Jun 2024The aim of this study is to evaluate the influence of implementation of the BFR training on the hypertrophy and strength of the lower limb muscles in combat sports...
BACKGROUND
The aim of this study is to evaluate the influence of implementation of the BFR training on the hypertrophy and strength of the lower limb muscles in combat sports fighters, using common and easy to perform both training and control methods.
METHODS
Design as a randomized control trial (RCT). The study included 30 men, MMA fighters since at least a year. They were divided into two groups: (A, a control group; B, men with the BFR training). The training lasted 8 weeks (3 times a week) and consisted of performing a set of specific exercises with a load of 20% 1RM.
RESULTS
The Wilcoxon analyzing test showed important changes in muscle girth (P<0.01) and lower limb muscular strength (P<0.05). These changes were to be seen in the tested group only, not in the control group.
CONCLUSIONS
Occlusion training is effective in increasing strength and hypertrophy of lower limb muscles in martial arts fighters.
PubMed: 38888559
DOI: 10.23736/S0022-4707.24.15782-9 -
Frontiers in Cardiovascular Medicine 2024The kynurenine pathway (KP) serves as the primary route for tryptophan metabolism in most mammalian organisms, with its downstream metabolites actively involved in... (Review)
Review
The kynurenine pathway (KP) serves as the primary route for tryptophan metabolism in most mammalian organisms, with its downstream metabolites actively involved in various physiological and pathological processes. Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) serve as the initial and pivotal enzymes of the KP, with IDO playing important and intricate roles in cardiovascular diseases. Multiple metabolites of KP have been observed to exhibit elevated concentrations in plasma across various cardiovascular diseases, such as atherosclerosis, hypertension, and acute myocardial infarction. Multiple studies have indicated that kynurenine (KYN) may serve as a potential biomarker for several adverse cardiovascular events. Furthermore, Kynurenine and its downstream metabolites have complex roles in inflammation, exhibiting both inhibitory and stimulatory effects on inflammatory responses under different conditions. In atherosclerosis, upregulation of IDO stimulates KYN production, mediating aromatic hydrocarbon receptor (AhR)-induced exacerbation of vascular inflammation and promotion of foam cell formation. Conversely, in arterial calcification, this mediation alleviates osteogenic differentiation of vascular smooth muscle cells. Additionally, in cardiac remodeling, KYN-mediated AhR activation exacerbates pathological left ventricular hypertrophy and fibrosis. Interventions targeting components of the KP, such as IDO inhibitors, 3-hydroxyanthranilic acid, and anthranilic acid, demonstrate cardiovascular protective effects. This review outlines the mechanistic roles of KP in coronary atherosclerosis, arterial calcification, and myocardial diseases, highlighting the potential diagnostic, prognostic, and therapeutic value of KP in cardiovascular diseases, thus providing novel insights for the development and application of related drugs in future research.
PubMed: 38883986
DOI: 10.3389/fcvm.2024.1406856 -
Physiological Genomics Jun 2024To investigate inter-individual differences in muscle thickness of Rectus Femoris (MTRF) following 12 weeks of Resistance Training (RT) or High-Intensity Interval...
To investigate inter-individual differences in muscle thickness of Rectus Femoris (MTRF) following 12 weeks of Resistance Training (RT) or High-Intensity Interval Training (HIIT) to explore the genetic architecture underlying skeletal muscle hypertrophy and to construct predictive models. We conducted musculoskeletal ultrasound assessments of the MTRF response in 440 physically inactive adults after the 12-week exercise period. A Genome-wide Association study (GWAS) was employed to identify variants associated with MTRF response, separately for RT and HIIT. Utilizing polygenic predictor score (PPS), we estimated the genetic contribution to exercise-induced hypertrophy. Predictive models for MTRF response were constructed using Random Forest (RF), Support Vector Mac (SVM), and Generalized Linear Model (GLM) in 10 cross-validated approach. MTRF increased significantly after both RT (8.8%, P<0.05) and HIIT (5.3%, P<0.05), but with considerable inter-individual differences (RT: -13.5~38.4%, HIIT: -14.2%~30.7%). Eleven lead SNPs in RT and eight lead SNPs in HIIT were identified at a significance level of P<1×10. The PPS was associated with MTRF response, explaining 47.2% of the variation in response to RT and 38.3% of the variation in response to HIIT. Notably, the GLM and SVM predictive models exhibited superior performance in comparison to RF models (p<0.05), and the GLM demonstrated optimal performance with an AUC of 0.809 (95%CI:0.669-0.949). Factors such as PPS, baseline MTRF, and exercise protocol exerted influence on the MTRF response to exercise, with PPS being the primary contributor. The GLM and SVM predictive model, incorporating both genetic and phenotypic factors, emerged as promising tools for predicting exercise-induced skeletal muscle hypertrophy.
PubMed: 38881426
DOI: 10.1152/physiolgenomics.00019.2024 -
Trends in Molecular Medicine Jun 2024A healthy lifespan relies on independent living, in which active skeletal muscle is a critical element. The cost of not recognizing and acting earlier on unhealthy or... (Review)
Review
A healthy lifespan relies on independent living, in which active skeletal muscle is a critical element. The cost of not recognizing and acting earlier on unhealthy or aging muscle could be detrimental, since muscular weakness is inversely associated with all-cause mortality. Sarcopenia is characterized by a decline in skeletal muscle mass and strength and is associated with aging. Exercise is the only effective therapy to delay sarcopenia development and improve muscle health in older adults. Although numerous interventions have been proposed to reduce sarcopenia, none has yet succeeded in clinical trials. This review evaluates the biological gap between recent clinical trials targeting sarcopenia and the preclinical studies on which they are based, and suggests an alternative approach to bridge the discrepancy.
PubMed: 38880726
DOI: 10.1016/j.molmed.2024.05.016 -
Journal of Pharmacological Sciences Aug 2024The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart...
The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5'-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (HS), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while HS accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.
Topics: Animals; Myocytes, Cardiac; Sulfides; Hydrogen Sulfide; Cells, Cultured; Ventricular Remodeling; Adenosine Triphosphate; Rats; Atrophy; Cardiomegaly; Heart Failure; Animals, Newborn; Rats, Sprague-Dawley
PubMed: 38880546
DOI: 10.1016/j.jphs.2024.05.002