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Frontiers in Endocrinology 2024X-linked hypophosphatemia (XLH) is caused by an inactivating mutation in the phosphate-regulating endopeptidase X-linked () gene whose defective product fails to control... (Observational Study)
Observational Study
INTRODUCTION
X-linked hypophosphatemia (XLH) is caused by an inactivating mutation in the phosphate-regulating endopeptidase X-linked () gene whose defective product fails to control phosphatonin fibroblast growth factor 23 (FGF23) serum levels. Although elevated FGF23 levels have been linked with detrimental cardiac effects, the cardiologic outcomes in XLH patients have been subject to debate. Our study aimed to evaluate the prevalence and severity of cardiovascular morbidity in pediatric XLH patients before, during, and after a 2-year treatment period with burosumab, a recombinant anti-FGF23 antibody.
METHODS
This prospective observational study was conducted in a tertiary medical center, and included 13 individuals with XLH (age range 0.6-16.2 years) who received burosumab every 2 weeks. Clinical assessment at treatment initiation and after .5, 1, and 2 years of uninterrupted treatment included anthropometric measurements and cardiologic evaluations (blood pressure [BP], electrocardiogram, conventional echocardiography, and myocardial strain imaging).
RESULTS
The linear growth of all patients improved significantly (mean height z-score: from -1.70 ± 0.80 to -0.96 ± 1.08, =0.03). Other favorable effects were decline in overweight/obesity rates (from 46.2% to 23.1%) and decreased rates of elevated BP (systolic BP from 38.5% to 15.4%; diastolic BP from 38.5% to 23.1%). Electrocardiograms revealed no significant abnormality throughout the study period. Cardiac dimensions and myocardial strain parameters were within the normative range for age at baseline and remained unchanged during the study period.
CONCLUSION
Cardiologic evaluations provided reassurance that 2 years of burosumab therapy did not cause cardiac morbidity. The beneficial effect of this treatment was a reduction in cardiovascular risk factors, as evidenced by the lower prevalence of both overweight/obesity and elevated BP.
Topics: Humans; Child; Adolescent; Male; Familial Hypophosphatemic Rickets; Fibroblast Growth Factor-23; Child, Preschool; Prospective Studies; Infant; Female; Antibodies, Monoclonal, Humanized; Cardiovascular Diseases; Follow-Up Studies; Fibroblast Growth Factors
PubMed: 38818505
DOI: 10.3389/fendo.2024.1400273 -
Journal of Cardiovascular Echography 2024Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and...
Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism.
PubMed: 38818313
DOI: 10.4103/jcecho.jcecho_4_24 -
Annals of Pediatric Cardiology 2023Childhood obesity has become a global concern, with its prevalence steadily increasing over the past decade. This condition negatively impacts the cardiovascular system,...
BACKGROUND
Childhood obesity has become a global concern, with its prevalence steadily increasing over the past decade. This condition negatively impacts the cardiovascular system, increasing the risk of morbidity and mortality in adulthood. This study aimed to identify cardiac function abnormalities and related risk factors among overweight and obese Thai children.
MATERIALS AND METHODS
A cross-sectional observational study of 70 children with body mass index (BMI) >1 standard deviation above the mean for Thai children was conducted at Naresuan University Hospital. Body fat percentage (%Fat) was measured, and standard transthoracic echocardiography was performed. Metabolic profiles were collected from medical records.
RESULTS
The thickness and diameter of the Left ventricle (LV) wall, including the LV posterior wall, LV internal diameter, and interventricular septum (IVS), were significantly increased in both systolic and diastolic phases in obese children. LV concentric hypertrophy and an abnormal E/E' ratio were found in 27% and 34.3% of participants, respectively. Right ventricular systolic dysfunction indicated by abnormal tricuspid annular plane systolic excursion values was found in 55.7% of all participants. In addition, 27.1% of all obese children had pulmonary hypertension. Significant differences in BMI and %Fat were detected between children with abnormal and normal IVS diastolic (IVSd) ( = 0.016). Our univariate and multivariate correlation analyses revealed a significant positive association between abnormal IVSd and %Fat, with an odd ratio (OR) of 1.13 (95% confidence interval [CI]: 1.01-1.27; = 0.047) and an adjusted OR of 1.17 (95% CI: 1.01-1.36; = 0.04).
CONCLUSIONS
Cardiac function abnormalities in childhood obesity exhibit a significant positive correlation with BMI and various cardiac dimensions, including ventricular wall thickness. One important related risk factor for increased IVS thickness is %Fat. Therefore, multidisciplinary management of obesity should be initiated as early as possible to prevent future cardiovascular morbidity and mortality.
PubMed: 38817261
DOI: 10.4103/apc.apc_134_23 -
Scientific Reports May 2024Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant...
Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant and immune-enhancing effects, its role in PAH treatment and the underlying mechanisms remain unclear. The therapeutic effects of Cordycepin on rats with PAH were investigated using a monocrotaline (MCT)-induced rat model. The metabolic effects of Cordycepin were assessed based on the plasma metabolome. The potential mechanisms of Cordycepin in PAH treatment were investigated through transcriptome sequencing and validated in pulmonary artery smooth muscle cells (PASMC). Evaluations included hematoxylin and eosin staining for pulmonary vascular remodeling, CCK-8 assay, EDU, and TUNEL kits for cell viability, proliferation, and apoptosis, respectively, and western blot for protein expression. Cordycepin significantly reduced right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in PAH rats, and mitigated pulmonary vascular remodeling. Plasma metabolomics showed that Cordycepin could reverse the metabolic disorders in the lungs of MCT-induced PAH rats, particularly impacting linoleic acid and alpha-linolenic acid metabolism pathways. Transcriptomics revealed that the P53 pathway might be the primary pathway involved, and western blot results showed that Cordycepin significantly increased P53 and P21 protein levels in lung tissues. Integrated analysis of transcriptomics and metabolomics suggested that these pathways were mainly enriched in linoleic acid metabolism and alpha-linolenic acid metabolism pathway. In vitro experiments demonstrated that Cordycepin significantly inhibited the PDGFBB (PD)-induced abnormal proliferation and migration of PASMC and promoted PD-induced apoptosis. Meanwhile, Cordycepin enhanced the expression levels of P53 and P21 proteins in PD-insulted PASMC. However, inhibitors of P53 and P21 eliminated these effects of Cordycepin. Cordycepin may activate the P53-P21 pathway to inhibit abnormal proliferation and migration of PASMC and promote apoptosis, offering a potential approach for PAH treatment.
Topics: Animals; Deoxyadenosines; Rats; Male; Apoptosis; Pulmonary Arterial Hypertension; Cell Proliferation; Transcriptome; Metabolomics; Myocytes, Smooth Muscle; Monocrotaline; Pulmonary Artery; Rats, Sprague-Dawley; Disease Models, Animal; Vascular Remodeling; Tumor Suppressor Protein p53; Linoleic Acid; Hypertrophy, Right Ventricular; Gene Expression Profiling
PubMed: 38816406
DOI: 10.1038/s41598-024-62163-3 -
Arteriosclerosis, Thrombosis, and... Jul 2024Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging...
BACKGROUND
Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear.
METHODS
We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples.
RESULTS
Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF.
CONCLUSIONS
Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.
Topics: Animals; Heart Failure; Proteomics; Humans; Hypertension, Pulmonary; Stroke Volume; Male; Disease Models, Animal; Female; beta 2-Microglobulin; Mice, Inbred C57BL; Aged; Sirtuin 3; Muscle, Skeletal; Cell Proliferation; Middle Aged; Mice; Biomarkers; Mice, Knockout; Case-Control Studies; Pulmonary Artery; Vascular Remodeling; Endothelial Cells; Cell Movement; Cells, Cultured; Ventricular Function, Left
PubMed: 38813697
DOI: 10.1161/ATVBAHA.123.320270 -
Cureus May 2024A 37-year-old male with type two diabetes presented to the hospital with new-onset heart failure and renal dysfunction. His left ventricular (LV) ejection fraction was...
A 37-year-old male with type two diabetes presented to the hospital with new-onset heart failure and renal dysfunction. His left ventricular (LV) ejection fraction was less than 10%. Transthoracic echocardiography and cardiovascular magnetic resonance (CMR) imaging also revealed severe bicuspid aortic valve stenosis, dilated cardiomyopathy with LV hypertrophy, prominent LV trabeculations, and features suggestive of mild myocarditis with active inflammation. While myocarditis was suspected on CMR imaging, his mild degree of myocardial involvement did not explain the entirety of his clinical presentation, degree of LV dysfunction, or other structural abnormalities. An extensive work-up for his LV dysfunction was unremarkable for ischemic, metabolic, infiltrative, infectious, toxic, oncologic, connective tissue, and autoimmune etiologies. Genetic testing was positive for a () variant, which was deemed likely to be a unifying etiology underlying his presentation. The sarcomere gene allows beta-myosin expression in heart ventricles, with variants associated with hypertrophic and dilated cardiomyopathies, congenital heart diseases, myocarditis, and excessive trabeculation (formerly known as left ventricular noncompaction). This case highlights the diverse array of cardiac pathologies that can present with gene variants and reviews an extensive work-up for this unusual presentation of heart failure in a young patient.
PubMed: 38813076
DOI: 10.7759/cureus.61252 -
Growth Hormone & IGF Research :... Jun 2024Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to... (Review)
Review
OBJECTIVE
Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species.
DESIGN
A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed.
RESULTS
Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine.
CONCLUSION
Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.
Topics: Acromegaly; Cats; Humans; Animals; Insulin-Like Growth Factor I; Cat Diseases
PubMed: 38810595
DOI: 10.1016/j.ghir.2024.101595 -
Scientific Reports May 2024Previous investigations have highlighted notable variations in cardiovascular risk indicators associated with various professional categories. However, only a few...
Previous investigations have highlighted notable variations in cardiovascular risk indicators associated with various professional categories. However, only a few studies have examined structural and functional cardiac parameters using echocardiography within distinct occupational groups. Hence, this study endeavored to assess cardiac structural and functional parameters in three additional occupations: firefighters (FFs), police officers (POs), and office workers (OWs). This prospective study encompassed 197 male participants (97 FFs, 54 POs, and 46 OWs) from Germany. All participants underwent 2D and Doppler echocardiography in resting conditions; standard parasternal and apical axis views were employed to evaluate structural (diastolic and systolic) and functional (systolic and diastolic function, and strain) cardiac parameters. All three occupational groups exhibited a tendency towards septal hypertrophy. Notably, OWs exhibited the largest diastolic interventricular septum diameter (IVSd), at 1.33 ± 0.25 cm. IVSd significantly varied between POs and OWs (p = 0.000) and between POs and FFs (p = 0.025). Additionally, during diastole a substantially larger left ventricular posterior wall diameter (LVPWd) was observed in OWs compared to FFs (p = 0.001) and POs (p = 0.013). The left ventricular diastolic cavity diameter (LVIDd) and the left ventricular systolic cavity diameter (LVIDs) were significantly higher in POs than they were in FFs (LVIDd: p = 0.001; LVIDs: p = 0.009), and the LVIDd was notably higher in FFs (p = 0.015) and POs compared to OWs (p = 0.000). FFs exhibited significantly better diastolic function, indicated by higher diastolic peak velocity ratios (MV E/A ratio) and E/E' ratios, compared to POs (E/A ratio: p = 0.025; E/E' ratio: p = 0.014). No significant difference in diastolic performance was found between OWs and FFs. Significantly higher E'(lateral) values were noted in POs compared to FFs (p = 0.003) and OWs (p = 0.004). Ejection fraction did not significantly differ among FFs, POs, and OWs (p > 0.6). The left ventricular mass (LV Mass) was notably higher in POs than it was in FFs (p = 0.039) and OWs (p = 0.033). Strain parameter differences were notably improved in two- (p = 0.006) and four-chamber (p = 0.018) views for FFs compared to POs. Concentric remodeling was the predominant change observed in all three occupational groups. Significant differences in the presence of various forms of hypertrophy were observed in FFs, POs, and OWs (exact Fisher test p-values: FFs vs. OWs = 0.021, POs vs. OWs = 0.002). OWs demonstrated notably higher rates of concentric remodeling than FFs did (71.77% vs. 47.9%). This study underscores disparities in both functional and structural parameters in diverse occupational groups. Larger prospective studies are warranted to investigate and delineate differences in structural and functional cardiac parameters across occupational groups, and to discern their associated effects and risks on the cardiovascular health of these distinct professional cohorts.
Topics: Humans; Male; Cross-Sectional Studies; Adult; Middle Aged; Prospective Studies; Echocardiography; Echocardiography, Doppler; Firefighters; Heart Ventricles; Germany; Occupations; Diastole; Police; Heart; Workplace; Ventricular Function, Left; Working Conditions
PubMed: 38802474
DOI: 10.1038/s41598-024-62190-0 -
Iranian Journal of Basic Medical... 2024Right ventricular hypertrophy (RVH) often results in failure of the right ventricle or even the left ventricle. Rosmarinic acid (RA), a natural polyphenol, is commonly...
Rosmarinic acid ameliorates the complications of monocrotaline-induced right ventricular hypertrophy on the left ventricle: Investigating the signaling pathway of Wnt/β-catenin in the heart.
OBJECTIVES
Right ventricular hypertrophy (RVH) often results in failure of the right ventricle or even the left ventricle. Rosmarinic acid (RA), a natural polyphenol, is commonly found in Boraginaceae species and some species of ferns and hornworts. This study looked at how RA affects oxidative stress and left ventricular hemodynamic functions as well as RVH in monocrotaline (MCT) induced RVH model rats.
MATERIALS AND METHODS
To cause RVH, MCT (60 mg/kg) was intraperitoneally (IP) injected. Rats were given saline or RA (10, 15, and 30 mg/kg, gavage, over 21 days). In anesthetized rats, the lead II electrocardiogram was recorded. The hemodynamic functions of the isolated heart were measured using the Langendorff apparatus (at constant pressure). Investigations were made into the right ventricular hypertrophy index (RVHI), the activities of superoxide dismutase, catalase, glutathione, and Wnt and β-catenin gene expressions in the left ventricle. H&E staining was used.
RESULTS
A significant decline in electrocardiogram parameters and anti-oxidant enzyme activities, an increase in QTc (Q-T corrected) intervals, MDA (Malondialdehyde), RVHI, and Wnt/β-catenin gene expression, and also significant changes in the hemodynamic parameters were demonstrated in the MCT group. RA improved the above-mentioned factors.
CONCLUSION
According to the findings, RA may act as a cardioprotective agent against cardiovascular complications brought on by RVH due to its capacity to boost the activity of cardiac anti-oxidant enzymes and decrease the expression of genes involved in vascular calcification.
PubMed: 38800027
DOI: 10.22038/IJBMS.2024.75201.16301 -
PeerJ 2024We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension...
We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. < 0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, = 0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed , and . Several circadian clock LV genes were modulated differently by AngII between control and Ovx females ( and ). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.
Topics: Animals; Female; Angiotensin II; Disease Models, Animal; Mice; Hypertension; Mice, Inbred C57BL; Ovariectomy; Aging; Heart Ventricles; Menopause; Humans; Connective Tissue Growth Factor; Heart Atria; Collagen Type III
PubMed: 38799057
DOI: 10.7717/peerj.17434