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JACC. Advances Dec 2023Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction...
BACKGROUND
Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction (HFpEF) is unknown.
OBJECTIVES
The authors investigated the potential of EAT and RV quantification for obesity-related pathophysiology and risk stratification in obese HFpEF patients using cardiovascular magnetic resonance (CMR).
METHODS
A total of 150 patients (obese, body mass index ≥30 kg/m; n = 73, nonobese, body mass index <30 kg/m; n = 77) with a clinical diagnosis of HFpEF undergoing CMR were retrospectively identified. EAT volume surrounding both ventricles were quantified with manual delineation on cine images. Total RV volume (TRVV) was calculated as the sum of RV cavity and mass at end-diastole. The endpoint was the composite of all-cause mortality and first HF hospitalization.
RESULTS
During a median follow-up of 46 months, 39 nonobese patients (51%) and 32 obese patients (44%) experienced the endpoint. EAT was a prognostic biomarker regardless of obesity and was independently correlated with TRVV. In obese HFpEF, EAT correlated with RV longitudinal strain (r = 0.32, = 0.006), and increased amount of EAT and TRVV was associated with greater left ventricular end-diastolic eccentric index (r = 0.36, = 0.002). The integration of RV quantification into EAT provided improved risk stratification with a C-statistic increase from 0.70 to 0.79 in obese HFpEF. Obese patients with EAT<130 ml and TRVV<180 ml had low risk (annual event rate 3.2%), while those with increased EAT ≥130 ml and TRVV ≥180 ml had significantly higher risk (annual event rate 11.8%; < 0.001).
CONCLUSIONS
CMR quantification of EAT and RV structure provides additive risk stratification for adverse outcomes in obese HFpEF.
PubMed: 38938495
DOI: 10.1016/j.jacadv.2023.100730 -
JACC. Advances Dec 2023
PubMed: 38938481
DOI: 10.1016/j.jacadv.2023.100731 -
Nature Communications Jun 2024Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity...
Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.
Topics: Intra-Abdominal Fat; Animals; Obesity; Humans; Neutrophils; Diet, High-Fat; Mice; Inflammation; Gastrointestinal Microbiome; Male; Mice, Inbred C57BL; Female; Feces; Microbiota; Th1 Cells; Neutrophil Infiltration
PubMed: 38937454
DOI: 10.1038/s41467-024-48935-5 -
Biochemical and Biophysical Research... Jun 2024Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix. It plays a pivotal role in the formation of the provisional matrix. S100a4, previously...
Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix. It plays a pivotal role in the formation of the provisional matrix. S100a4, previously known as fibroblast-specific protein, functions as a calcium channel-binding protein. To investigate the role of versican expressed in fibroblasts, we generated conditional knockout mice in which versican expression is deleted in cells expressing S100a4. We found that S100a4 is expressed in adipose tissues, and these mice exhibit obesity under a normal diet, which becomes apparent as early as five months. The white adipose tissues of these mice exhibited decreased expression levels of S100a4 and versican and hypertrophy of adipocytes. qRT-PCR showed a reduced level of UCP1 in their white adipose tissues, indicating that the basic energy metabolism is diminished. These results suggest that versican in adipose tissues maintains the homeostasis of adipose tissues and regulates energy metabolism.
PubMed: 38936224
DOI: 10.1016/j.bbrc.2024.150309 -
Biomedicine & Pharmacotherapy =... Jun 20241,25(OH)D is a fat-soluble vitamin, involved in regulating Ca homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is... (Review)
Review
BACKGROUND
1,25(OH)D is a fat-soluble vitamin, involved in regulating Ca homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH)D blood level. In addition, 1,25(OH)D plays vital roles in Ca-P and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes.
SCOPE AND APPROACH
The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH)D-deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery.
KEY FINDINGS AND CONCLUSIONS
Several studies have revealed that cancer development in a background of 1,25(OH)D deficient obesity involves the VDR gene. Moreover, 1,25(OH)D is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH)D-based therapies without any side effects.
PubMed: 38936194
DOI: 10.1016/j.biopha.2024.117001 -
Journal of Food and Drug Analysis Jun 2024We aimed to investigate the therapeutic potential of ibuprofen against type 2 diabetes (T2D) using obese Zucker diabetic fatty (ZDF) rats as type 2 diabetes model. ZDF...
We aimed to investigate the therapeutic potential of ibuprofen against type 2 diabetes (T2D) using obese Zucker diabetic fatty (ZDF) rats as type 2 diabetes model. ZDF rats were hyperglycemic, dyslipidemic and expressed proinflammatory markers in contrast to lean controls, thus reflecting the relationship between obesity and chronic inflammation promoting T2D. Chronic treatment with ibuprofen (2-(4-Isobutylphenyl)propanoic acid) was used to study the impact on pathological T2D conditions as compared to metformin (1,1-dimethylbiguanide) treated ZDF as well as lean controls. Ibuprofen decreased A1c but induced a high insulin release with improved glucose tolerance only after early time points (i.g., 15 and 30 min) resulting in a non-significant decline of AUC values and translating into a high HOMA-IR. In addition, ibuprofen significantly lowered cholesterol, free fatty acids and HDL-C. Some of these effects by ibuprofen might be based on its anti-inflammatory effects through inhibition of cytokine/chemokine signaling (i.g., COX-2, ICAM-1 and TNF-α) as measured in whole blood and epididymal adipose tissue by TaqMan and/or upregulation of anti-inflammatory cytokines (i.g., IL-4 and IL-13) by ELISA analysis in blood. In conclusion, our ZDF animal study showed positive effects of ibuprofen against diabetic complications such as inflammation and dyslipidemia but also demonstrated the risk of causing insulin resistance.
Topics: Animals; Rats, Zucker; Diabetes Mellitus, Type 2; Ibuprofen; Rats; Male; Blood Glucose; Humans; Disease Models, Animal; Insulin; Obesity; Cytokines; Insulin Resistance
PubMed: 38934691
DOI: 10.38212/2224-6614.3506 -
Cytotechnology Aug 2024Cardiovascular diseases remain as the most common cause of death worldwide. To reveal the underlying mechanisms in varying cardiovascular diseases, in vitro models with...
UNLABELLED
Cardiovascular diseases remain as the most common cause of death worldwide. To reveal the underlying mechanisms in varying cardiovascular diseases, in vitro models with cells and supportive biomaterial can be designed to recapitulate the essential components of human heart. In this study, we analyzed whether 3D co-culture of cardiomyocytes (CM) with vascular network and with adipose tissue-derived mesenchymal stem/stromal cells (ASC) can support CM functionality. CM were cultured with either endothelial cells (EC) and ASC or with only ASC in hydrazide-modified gelatin and oxidized gellan gum hybrid hydrogel to form cardiovascular multiculture and myocardial co-culture, respectively. We studied functional characteristics of CM in two different cellular set-ups and analyzed vascular network formation, cellular morphology and orientation. The results showed that gellan gum-gelatin hydrogel supports formation of two different cellular networks and functional CM. We detected formation of a modest vascular network in cardiovascular multiculture and extensive ASC-derived alpha smooth muscle actin -positive cellular network in multi- and co-culture. iPSC-CM showed elongated morphology, partly aligned orientation with the formed networks and presented normal calcium transients, beating rates, and contraction and relaxation behavior in both setups. These 3D cardiac models provide promising platforms to study (patho) physiological mechanisms of cardiovascular diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10616-024-00630-5.
PubMed: 38933872
DOI: 10.1007/s10616-024-00630-5 -
Frontiers in Medicine 2024Quantitative computed tomography (CT) analysis is an important method for diagnosis and severity evaluation of lung diseases. However, the association between CT-derived...
PURPOSE
Quantitative computed tomography (CT) analysis is an important method for diagnosis and severity evaluation of lung diseases. However, the association between CT-derived biomarkers and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. We aimed to investigate its potential in predicting COPD exacerbations.
METHODS
Patients with COPD were consecutively enrolled, and their data were analyzed in this retrospective study. Body composition and thoracic abnormalities were analyzed from chest CT scans. Logistic regression analysis was performed to identify independent risk factors of exacerbation. Based on 2-year follow-up data, the deep learning system (DLS) was developed to predict future exacerbations. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance. Finally, the survival analysis was performed to further evaluate the potential of the DLS in risk stratification.
RESULTS
A total of 1,150 eligible patients were included and followed up for 2 years. Multivariate analysis revealed that CT-derived high affected lung volume/total lung capacity (ALV/TLC) ratio, high visceral adipose tissue area (VAT), and low pectoralis muscle cross-sectional area (CSA) were independent risk factors causing COPD exacerbations. The DLS outperformed exacerbation history and the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, with an area under the ROC (AUC) value of 0.88 (95%CI, 0.82-0.92) in the internal cohort and 0.86 (95%CI, 0.81-0.89) in the external cohort. The DeLong test revealed significance between this system and conventional scores in the test cohorts ( < 0.05). In the survival analysis, patients with higher risk were susceptible to exacerbation events.
CONCLUSION
The DLS could allow accurate prediction of COPD exacerbations. The newly identified CT biomarkers (ALV/TLC ratio, VAT, and pectoralis muscle CSA) could potentially enable investigation into underlying mechanisms responsible for exacerbations.
PubMed: 38933101
DOI: 10.3389/fmed.2024.1370917 -
Journal of Diabetes and Metabolic... Jun 2024The aim of this article is to provide an insight into the role of obesity as a risk factor, and as a potential etiologic agent of atrial fibrillation (AF) and heart... (Review)
Review
OBJECTIVES
The aim of this article is to provide an insight into the role of obesity as a risk factor, and as a potential etiologic agent of atrial fibrillation (AF) and heart failure (HF).
METHODS
A narrative (non-systematic) review article summarizing currently available data regarding the interaction between obesity, AF and HF.
RESULTS
Obesity is considered a risk factor of AF and chronic HF. Multiple recent studies indicate that obesity is also a potential causal factor in the development of AF and HF, the elucidation of pathological mechanisms of which could help devise new diagnostic and therapeutic modalities for these conditions. The discussion about obesity in relation to HF cannot omit the so-called obesity paradox, which represents a dilemma for clinicians, and it is still a source of irregularities regarding the strategy of weight reduction in obese patients with HF. Recently, the obesity paradox has also been assumed to play a role in the relationship between obesity and thromboembolic complications of AF.
CONCLUSIONS
Obesity is an independent and modifiable risk factor for AF and HF. In addition, there is an increasing volume of experimental and clinical data that suggests an important role of the epicardial adipose tissue in the pathophysiology of AF. However, several issues, such as the issue of optimal pharmacotherapy and weight reduction strategy in obese patients with HF remains still unanswered, and open for future investigation.
PubMed: 38932866
DOI: 10.1007/s40200-023-01332-z -
Archivum Immunologiae Et Therapiae... Jan 2024Rheumatoid arthritis (RA) is a complex autoimmune disease that leads to joint destruction. A number of immune cells that affect joint tissues are involved in the...
Rheumatoid arthritis (RA) is a complex autoimmune disease that leads to joint destruction. A number of immune cells that affect joint tissues are involved in the pathogenesis of this disease. This leads to the synthesis of many pro-inflammatory mediators. The transport of drugs, as well as many cytokines involved in the development of inflammation in RA patients, is mediated by membrane transporters. Membrane transporters are proteins that mediate the transfer of substrates across biological membranes. But to date there are no studies examining the expression of solute carrier (SLC) transporters in joint tissues. The aim of the study was to evaluate the expression of individual SLC family transporters in the synovial membranes (SMs) and infrapatellar fat pad (Hoffa's pad) of RA patients. The study included 20 patients with rheumatoid arthritis and 20 with osteoarthritis as the control group who were undergoing joint replacement surgery as a normal part of clinical care. In the SM and Hoffa's pad of RA patients the following 17 membrane transporters were defined at relevant expression levels for SLC transporter superfamily: . The confirmed expression of these transporters in the SMs as well as Hoffa's pad of patients with RA and OA, and the differences in their expression between these groups, suggests the involvement of SLC transporters in both the maintenance of homeostasis under physiological conditions in the tissues of the joints, as well as in the inflammatory process in RA.
Topics: Humans; Arthritis, Rheumatoid; Female; Synovial Membrane; Middle Aged; Solute Carrier Proteins; Male; Aged; Adipose Tissue; Adult; Membrane Transport Proteins; Biological Transport; Osteoarthritis
PubMed: 38932672
DOI: 10.2478/aite-2024-0014