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European Journal of Pharmacology Jun 2024Fenofibrate, a PPAR-α agonist clinically used to lower serum lipid levels, reduces cardiac remodeling and improves cardiac function. However, its mechanism of action is...
Fenofibrate, a PPAR-α agonist clinically used to lower serum lipid levels, reduces cardiac remodeling and improves cardiac function. However, its mechanism of action is not completely elucidated. In this study we examined the effect of fenofibrate on mitochondria in a rat model of renovascular hypertension, focusing on mediators controlling mitochondrial dynamics and autophagy. Rats with two-kidney one-clip (2K1C) hypertension were treated with fenofibrate 150 mg/kg/day (2K1C-FFB) or vehicle (2K1C-VEH) for 8 weeks. Systolic blood pressure and cardiac functional were in-vivo assessed, while cardiomyocyte size and protein expression of mediators of cardiac hypertrophy and mitochondrial dynamics were ex-vivo examined by histological and Western blot analyses. Fenofibrate treatment counteracted the development of hypertension and the increase of left ventricular mass, relative wall thickness and cross-sectional area of cardiomyocytes. Furthermore, fenofibrate re-balanced the expression Mfn2, Drp1 and Parkin, regulators of fusion, fission, mitophagy respectively. Regarding autophagy, the LC3-II/LC3-I ratio was increased in 2K1C-VEH and 2K1C-FFB, whereas the autophagy was increased only in 2K1C-FFB. In cultured H9C2 cardiomyoblasts, fenofibrate reversed the Ang II-induced mRNA up-regulation of hypertrophy markers Nppa and Myh7, accumulation of reactive oxygen species and depolarization of the mitochondrial membrane exerting protection mediated by up-regulation of the Uncoupling protein 2. Our results indicate that fenofibrate acts directly on cardiomyocytes and counteracts the pressure overload-induced cardiac maladaptive remodeling. This study reveals a so far hidden mechanism involving mitochondrial dynamics in the beneficial effects of fenofibrate, support its repurposing for the treatment of cardiac hypertrophy and provide new potential targets for its pharmacological function.
PubMed: 38909934
DOI: 10.1016/j.ejphar.2024.176767 -
Biochemical Pharmacology Jun 2024Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery...
Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular remodeling. Mesenchymal stem cell- derived exosomes (MSC-Exos) can relieve HPH by reversing pulmonary vascular remodeling. The HPH model was established in healthy male Sprague-Dawley (SD) rats aged 6 to 8 weeks. The rats were placed in a room with oxygen concentration of (10 ± 1) % for 8 h a day over 28 days, were then injected intravenously with MSC-Exos (100 ug protein/kg) or equal-volume phosphate buffer saline (PBS) once a day over 1 week. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling were observed after anesthesia. In addition, platelet-derived growth factor BB (PDGF-BB) were used to stimulate rat pulmonary artery smooth muscle cells (PASMCs) to construct HPH pathological cell models. The results showed that MSC-Exos could not only reduce the elevation of RVSP, right ventricular hypertrophy and the degree of pulmonary vascular remodeling in HPH rats, but also reduce the proliferation, migration and apoptosis resistance of PASMCs. Finally, GSE53408 and GSE113439 datasets were analyzed and showed that the expression of Hsp90aa1 and pERK/ERK were significantly increased in HPH, also could be inhibited by MSC-Exos. Meanwhile, inhibition of Hsp90aa1 also reduced PASMCs migration and pERK/ERK protein level. In conclusion, MSC-Exos alleviated HPH by suppressing PASMCs proliferation, migration and apoptosis resistance through inhibiting the Hsp90aa1/ERK/pERK pathway.
PubMed: 38909785
DOI: 10.1016/j.bcp.2024.116382 -
Biomedical Engineering Online Jun 2024Left ventricular enlargement (LVE) is a common manifestation of cardiac remodeling that is closely associated with cardiac dysfunction, heart failure (HF), and...
BACKGROUND
Left ventricular enlargement (LVE) is a common manifestation of cardiac remodeling that is closely associated with cardiac dysfunction, heart failure (HF), and arrhythmias. This study aimed to propose a machine learning (ML)-based strategy to identify LVE in HF patients by means of pulse wave signals.
METHOD
We constructed two high-quality pulse wave datasets comprising a non-LVE group and an LVE group based on the 264 HF patients. Fourier series calculations were employed to determine if significant frequency differences existed between the two datasets, thereby ensuring their validity. Then, the ML-based identification was undertaken by means of classification and regression models: a weighted random forest model was employed for binary classification of the datasets, and a densely connected convolutional network was utilized to directly estimate the left ventricular diastolic diameter index (LVDdI) through regression. Finally, the accuracy of the two models was validated by comparing their results with clinical measurements, using accuracy and the area under the receiver operating characteristic curve (AUC-ROC) to assess their capability for identifying LVE patients.
RESULTS
The classification model exhibited superior performance with an accuracy of 0.91 and an AUC-ROC of 0.93. The regression model achieved an accuracy of 0.88 and an AUC-ROC of 0.89, indicating that both models can quickly and accurately identify LVE in HF patients.
CONCLUSION
The proposed ML methods are verified to achieve effective classification and regression with good performance for identifying LVE in HF patients based on pulse wave signals. This study thus demonstrates the feasibility and potential of the ML-based strategy for clinical practice while offering an effective and robust tool for diagnosing and intervening ventricular remodeling.
Topics: Humans; Heart Failure; Machine Learning; Female; Male; Pulse Wave Analysis; Middle Aged; Aged; Signal Processing, Computer-Assisted; Hypertrophy, Left Ventricular
PubMed: 38909231
DOI: 10.1186/s12938-024-01257-5 -
Medicina 2024Fabry disease (FD) is an X-linked lysosomal storage disorder affecting glycosphingolipid metabolism. Most FD patients have cardiac involvement, mainly manifested as left... (Observational Study)
Observational Study
INTRODUCTION
Fabry disease (FD) is an X-linked lysosomal storage disorder affecting glycosphingolipid metabolism. Most FD patients have cardiac involvement, mainly manifested as left ventricular hypertrophy (LVH), leading to early death due to complications (arrhythmias, valvular disease, vascular involvement). Early initiation of enzyme replacement therapy (ERT) before fibrosis development has been associated with better cardiac outcomes in terms of left ventricular mass index (LVMI) and functional parameters.
METHODS
A retrospective observational study was conducted in patients with FD treated with agalsidase alfa for at least 2 years. The primary objectives were: [a] to assess the annual rate of change in LVMI; [b] to define the overall incidence of stability, regression or progression of LVMI.
RESULTS
Forty-nine patients were included in the final analysis, with a median follow-up of 7 years. The overall change in LVMI was 0.38 g/m2.73/year, without significant influence of baseline LVH, gender, age at ERT initiation, LV ejection fraction, body mass index, renal disease, and classical cardiovascular risk factors. Long-term ERT with agalsidase alfa was associated with stabilization of LVMI in 98% of patients with FD and was independent of the same covariables.
CONCLUSION
Our results are in line with previous literature of comparable FD populations and probably represent the first study of its kind in Argentina. We here highlight the importance of cardiac morphometric stability as a positive outcome of ERT.
Topics: Humans; Fabry Disease; Male; Female; Retrospective Studies; alpha-Galactosidase; Hypertrophy, Left Ventricular; Adult; Enzyme Replacement Therapy; Middle Aged; Isoenzymes; Recombinant Proteins; Treatment Outcome; Follow-Up Studies; Time Factors
PubMed: 38907966
DOI: No ID Found -
Medicina 2024The different structural modifications that have been described in the heart of the high-performance athlete depend on factors such as age, gender, type of sport, and... (Comparative Study)
Comparative Study
INTRODUCTION
The different structural modifications that have been described in the heart of the high-performance athlete depend on factors such as age, gender, type of sport, and the intensity and time dedicated to training.
OBJECTIVES
Evaluation of elite athletes through echocardiography for the description of cardiac structure and function, and the comparison between athletes with cardiorespiratory endurance and the rest of the athletes.
METHODS
We performed the echocardiographic examination in 224 elite athletes, 96 women and 128 men aged 15 to 38 years (21.7 ± 5.3 years) and they were divided into 2 groups: "Endurance Group" (cardiorespiratory endurance) and "Non-Endurance Group" which included the rest of the sports. Univariate comparison between the two groups was performed by measuring 14 echocardiographic variables.
RESULTS
In men, statistically significant higher values were identified in the endurance group for interventricular septum, left ventricular posterior wall, relative wall thickness (RWT), left ventricular mass index and left atrial dimension. In women, the endurance group had significantly lower heart rate values, and significantly higher left ventricular diastolic dimension with normal RWT.
CONCLUSIONS
Most of the echocardiographic variables showed higher sample means in the endurance athletes. In the subgroup of men from the Endurance Group, eccentric hypertrophy prevailed with a greater increase in wall thickness, as well as in the diameter of the left atrium, while in women the variables indicated eccentric hypertrophy at the expense of an increase in left ventricle diameter, without increased wall thickness.
Topics: Humans; Male; Female; Adult; Physical Endurance; Young Adult; Echocardiography; Adolescent; Athletes; Adaptation, Physiological; Heart Rate; Sex Factors; Heart Ventricles
PubMed: 38907955
DOI: No ID Found -
Pediatric Nephrology (Berlin, Germany) Jun 2024
PubMed: 38907783
DOI: 10.1007/s00467-024-06439-w -
The Journal of Pharmacology and... Jun 2024
Topics: Humans; Hypertrophy, Left Ventricular; Blood Pressure; Antihypertensive Agents; Hypertension
PubMed: 38906565
DOI: 10.1124/jpet.123.002093 -
International Journal of Surgery... Jun 2024The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after...
OBJECTIVE
The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis.
METHODS
We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors.
RESULTS
17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation (HR:5.634, 95%CI:1.663-19.086, P=0.005), Noonan syndrome (HR:3.770, 95%CI:1.245-11.419, P=0.019), preoperational systolic anterior motion (SAM)(HR:4.596, 95%CI:1.532-13.792, P=0.007)and mid-ventricular obstruction (HR:4.763, 95%CI:1.538-14.754, P=0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior (P=0.014), mid-inferoseptal(P=0.044), mid-inferior(P=0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis.
CONCLUSION
Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.
PubMed: 38905490
DOI: 10.1097/JS9.0000000000001862 -
The International Journal of Artificial... Jun 2024To investigate the effects of different blood purification modes on left ventricular remodeling and its relationship with serum cardiac troponin I (cTnI) in patients...
OBJECTIVE
To investigate the effects of different blood purification modes on left ventricular remodeling and its relationship with serum cardiac troponin I (cTnI) in patients with end-stage renal disease (ESRD).
METHOD
A total of 108 patients with ESRD were selected, 55 cases were divided into hemodialysis combined with hemoperfusion (HD + HP) group, in which patients participants accepted routine hemodialysis for three times/week and hemoperfusion for three times/month; 53 cases in hemodialysis combined with hemodialysis filtration (HD + HDF) group, routine hemodialysis three times/week + hemodialysis filtration three times/month. The total duration of dialysis in the study was 1 year. Cardiac troponin I (cTnI) levels were measured before dialysis and 1 year after treatment, and related parameters were measured by echocardiography, including ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), and left ventricular myocardial mass index (LVMI). The paired test was used within the group. Correlation analysis was performed using Spearman correlation analysis.
RESULT
After treatment, the levels of cTnI, IVST, LVPWT, LVEDd, LVEDs, and LVMI in the two groups were increased, and the results were statistically significant (all < 0.05). In addition, cTnI of the two groups was significantly correlated with IVST, LVPWT, LVEDd, LVEDs, and LVMI (all < 0.05).
CONCLUSION
Left ventricular remodeling is common in patients with ESRD, HD + Hp, and HD + HDF cannot reduce the phenomenon of left ventricular remodeling, cTnI can be used as a predictor of left ventricular hypertrophy and enlargement.
PubMed: 38904358
DOI: 10.1177/03913988241259975 -
SAGE Open Medical Case Reports 2024Midventricular obstruction (MVO) is a rare form of hypertrophic cardiomyopathy (HCM). While surgical treatment for HCM is among the most technically challenging cardiac...
Midventricular obstruction (MVO) is a rare form of hypertrophic cardiomyopathy (HCM). While surgical treatment for HCM is among the most technically challenging cardiac operations for acquired disease, surgery for MVO is rarely reported. A 38-year-old man was admitted to our hospital with a cough and dyspnea. Transthoracic and transesophageal echography and computed tomography revealed extensive left ventricular hypertrophy, extending from the anteroseptal wall to the apex, and marked papillary muscle hypertrophy. We underwent septal myectomy via aortotomy (Morrow procedure) and apical surgery. Extended myectomy provides the best exposure to the hypertrophied septum and improves the functional status of patients.
PubMed: 38903183
DOI: 10.1177/2050313X241263704