Publications by authors named "Antonella De Angelis"
Background: Human cardiac organoids closely replicate the architecture and function of the human heart, offering a potential accurate platform for studying cellular and molecular features of aging cardiomyopathy. Senolytics have shown potential in addressing age-related pathologies but their potential to reverse aging-related human cardiomyopathy remains largely unexplored.
Methods: We employed human iPSC-derived cardiac organoids (hCOs/hCardioids) to model doxorubicin(DOXO)-induced cardiomyopathy in an aged context.
Article Synopsis
- Heart failure (HF) is a significant global health issue, especially for the aging population; this study investigates the drug sacubitril/valsartan's effects on aging-related HF with preserved ejection fraction (HFpEF) in rats.
- After 12 weeks of treatment, both sacubitril/valsartan and valsartan showed improvements in cardiac hypertrophy, evidenced by reduced heart muscle thickness, but neither treatment effectively reduced myocardial fibrosis or corrected diastolic dysfunction.
- The study indicates that while the treatments positively impacted heart muscle size and activated cardioprotective signaling pathways, challenges like inflammation and oxidative stress remained unaddressed, leaving diastolic dysfunction and fibrosis in aging hearts.
Article Synopsis
- Aging leads to sarcopenia, characterized by loss of muscle strength and increased fatigue, partially due to reduced essential amino acid intake affecting muscle health.
- A study shows that branched-chain amino acid (BCAA) supplements can improve muscle weakness and atrophy in aged mice, particularly when combined with L-alanine.
- Findings indicate that calcium homeostasis is disrupted in aged muscles, but BCAAs, especially the BCAAs+L-alanine combination, can restore some of these calcium-related dysfunctions, highlighting their potential in addressing age-related muscle decline.
Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, anti-diabetic drugs in heart failure and cognitive impairment: potential mechanisms of the protective effects.
Maria Antonietta Riemma Elena Mele Maria Donniacuo Marialucia Telesca Gabriella Bellocchio Antonella De Angelis
Front Pharmacol
June 2024
Article Synopsis
- Heart failure and cognitive impairment are significant public health issues, especially as the global population ages, with strong links to age and multiple health issues.
- Type 2 diabetes increases risks for both heart and brain health, promoting conditions like heart failure and cognitive decline due to its metabolic complications.
- New anti-diabetic medications, such as GLP-1R agonists and SGLT2 inhibitors, show promise in reducing the risk of cardiovascular and neurological issues beyond just controlling blood sugar, but further research is needed to fully understand their mechanisms.
Article Synopsis
- - The study investigates whether illegal toxic waste discharge can cause a new reproductive condition called morpho-epigenetic pathozoospermia in young men who typically have normal sperm quality.
- - Findings reveal that exposure to environmental contaminants can lead to serious sperm defects and an increase in low-quality circular RNA in the seminal plasma of men living in heavily polluted areas.
- - The research involved semen samples from 160 healthy men, split between those from a contaminated region in Italy ('Land of Fires') and a control group, highlighting significant differences in sperm quality attributed to environmental pollution.
Article Synopsis
- Doxorubicin (DOX), a cancer treatment, causes cardiotoxicity, with early signs showing as diastolic dysfunction and fibrosis.
- Researchers found that cardiac fibroblasts (CFs) become activated soon after DOX treatment, leading to increased metabolic activity and a shift towards glycolytic energy production.
- The changes in CFs are linked to myofibroblast differentiation and pro-fibrotic signaling, suggesting that targeting these early CF responses could help mitigate the heart damage caused by anthracycline drugs like DOX.
Article Synopsis
- Three-dimensional (3D) cell culture systems, especially stem-cell-derived spheroids, are increasingly recognized for their ability to better replicate in vivo conditions and support cardiac regeneration.* -
- This study evaluated three scaffold-free 3D culture methods: ultra-low attachment plates, hanging drops, and agarose micro-molds, finding that moving from 2D to 3D culture enhances cardiac stem cell differentiation into cardiomyocytes.* -
- Results showed that using agarose micro-molds for 3D culture optimally promotes cardiomyocyte yields, suggesting that 3D culture systems are effective models for studying cardiac regeneration.*
Article Synopsis
- - Atrial fibrillation (AF) has been noted in COVID-19 patients and reports suggest a possible but unclear link between AF and COVID-19 vaccinations, prompting a thorough analysis of related reports in the European pharmacovigilance database from 2020 to November 2022.
- - The study reviewed 6,226 reports of AF, which constituted only 0.3% of all vaccine-related reports, predominantly affecting adults, especially those over 65, and was commonly associated with the mRNA vaccines: tozinameran (54%), elasomeran (28.3%), and ChAdOx1-S (14.32%).
- - Although hospitalization was required for 35% of the AF cases, and
Appropriate dilated cardiomyopathy (DCM) animal models are highly desirable considering the pathophysiological and clinical heterogeneity of DCM. Genetically modified mice are the most widely and intensively utilized research animals for DCM. However, to translate discoveries from basic science into new and personalized medical applications, research in non-genetically based DCM models remains a key issue.
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- Nuclear F-actin in sperm cells is vital for supporting the acroplaxome and ensuring the correct positioning of the sperm membrane protein IZUMO1, crucial for sperm-oocyte fusion.
- The study compares high-quality (A-SPZ) and low-quality (B-SPZ) human spermatozoa, revealing that excessive F-actin in B-SPZ altered the localization of IZUMO1.
- F-actin depolymerization, induced by a treatment called cytochalasin D, improved both IZUMO1 repositioning and acrosome reaction, while promoting better sperm nuclear size and histone acetylation, suggesting F-actin's significant role in sperm quality control.
Article Synopsis
- * COVID-19 can lead to a prothrombotic state, which increases the likelihood of arrhythmias, partly due to the interaction of the virus with angiotensin-converting enzyme 2 (ACE2), causing adverse effects on heart health.
- * Certain medications used to treat COVID-19, like azithromycin and remdesivir, may increase the risk of cardiac dysfunction and arrhythmias, highlighting the need for careful management of cardiovascular safety in these patients.
Article Synopsis
- - The study investigates how type 1 and type 2 diabetes, induced by streptozotocin (STZ), affect heart structure and function in mice, revealing key differences in cardiac health between the two diabetes types.
- - Type 1 diabetes (T1DM) led to more severe heart issues, including increased cell death and stress in heart cells compared to type 2 diabetes (T2DM).
- - The findings highlight that T1DM and T2DM cause distinct changes in heart performance and gene expression, emphasizing the need to choose the right animal model for researching diabetic heart conditions.
Article Synopsis
- Cardiorenal syndrome involves heart and kidney issues that often arise from shared risk factors like hypertension and diabetes.
- A study on dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, showed it can improve kidney function and reduce markers of renal damage in a non-diabetic model of cardiorenal disease.
- The drug worked by decreasing inflammation, oxidative stress, and modifying the renin-angiotensin-aldosterone system, suggesting it offers protective benefits for renal health.
Article Synopsis
- * This class includes five medications: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin, which may also provide benefits for heart and kidney health.
- * While generally well-tolerated, SGLT2 inhibitors can have serious side effects such as hypoglycemia, infections, and other complications, necessitating careful patient monitoring.
Cardiovascular diseases (CVD) are predominantly an aging disease. Important sex-specific differences exist and the mechanism(s) by which this sex-by-age interaction influences CVD development and progression remains elusive. Accordingly, it is still unknown whether cell senescence, a main feature of cardiac male aging, is a significant feature also of the female aged mouse heart and whether senolytics, senescence-clearing compounds, promote myocardial repair and regeneration after myocardial infarction (MI) in aged female mice.
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- * SGLT2 inhibitors, a new class of diabetes medications, have shown unexpected benefits in reducing cardiovascular deaths and may help slow down atherosclerosis progression by targeting inflammation.
- * This review discusses how SGLT2 inhibitors can control blood sugar levels and also potentially reduce inflammation related to atherosclerosis, offering dual benefits for patients.
Article Synopsis
- * The study investigated Ranolazine, a metabolic modulator, in aged mice to see if it could improve muscle function and strength.
- * Results showed that Ranolazine boosted muscle strength and promoted positive changes in muscle structure and gene expression, along with enhancing antioxidant systems, suggesting it may help address muscle deterioration in the elderly.
Article Synopsis
- Heart failure, primarily due to the loss or dysfunction of heart muscle cells (cardiomyocytes), is a leading cause of death worldwide, sparking interest in myocardial regeneration techniques for heart repair.
- The field has experienced both advancements and setbacks, with ongoing debates about the heart's regenerative abilities and a mix of successes and failures in translating lab findings to real-world treatments.
- The research delves into existing and promising future regenerative methods, including those still in experimental stages, to provide insight into improving heart failure management and treatment approaches.
Article Synopsis
- A pharmacovigilance study analyzed reports of myocarditis and pericarditis associated with mRNA COVID-19 vaccines in the VAERS database from 1990 to July 2021, finding significant cases linked primarily to these vaccines.
- The majority of reported cases were in young males, particularly after the second vaccine dose, but the overall risk of these heart conditions was much lower compared to the risks from COVID-19 infection and common viral myocarditis.
- Compared to smallpox vaccines, the study found that mRNA COVID-19 vaccines had a significantly lower probability of causing myocarditis or pericarditis.
Article Synopsis
- Innovation in a clinical context involves introducing new or significantly improved products, processes, or services to enhance quality, efficacy, and safety of treatments, especially in rhinology.
- Modern pharmacological innovations, particularly biological drugs like monoclonal antibodies, target specific inflammation pathways for conditions affecting the nasal cavities and sinuses, showing promise in treating inflammatory, infectious, and cancerous diseases.
- Advanced technologies such as artificial intelligence and mobile health tools enhance precision medicine and treatment monitoring, improving patient outcomes and quality of life in rhinologic care.
Article Synopsis
- Dapagliflozin has been linked to an increased risk of diabetic ketoacidosis, leading to its withdrawal for treating type 1 diabetes in Europe, but it’s still prescribed for type 2 diabetes.
- A study analyzed reports of ketoacidosis events associated with dapagliflozin using the European spontaneous reporting system and found 2,406 cases, with diabetic ketoacidosis being the most common occurrence.
- Dapagliflozin had a significantly higher reporting frequency of ketoacidosis compared to DPP-4 inhibitors and insulins, indicating that healthcare providers should monitor patients on this medication closely.
Article Synopsis
- Cardiomyopathy is a frequent issue for diabetic patients, caused by factors like high blood sugar and insulin levels, leading to heart cell death and dysfunction.
- The diabetic heart undergoes aging and struggles with cell replacement due to chronic inflammation and stress affecting cardiac stem cells.
- Improving stem cell health and function in the diabetic heart could be key therapeutic targets, though many treatment strategies still need testing.
Diabetes mellitus (DM) affects the biology of multipotent cardiac stem/progenitor cells (CSCs) and adult myocardial regeneration. We assessed the hypothesis that senescence and senescence-associated secretory phenotype (SASP) are main mechanisms of cardiac degenerative defect in DM. Accordingly, we tested whether ablation of senescent CSCs would rescue the cardiac regenerative/reparative defect imposed by DM.
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- Type 2 diabetes and heart failure share common risk factors, such as obesity and inflammation, leading to similar underlying issues like endothelial dysfunction and oxidative stress.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular benefits not just through their effects on diabetes but also via unique cardiac mechanisms impacting ion balance, cell death, and inflammation.
- Current research emphasizes how reducing intracellular sodium levels enhances calcium handling, improving heart function and has antiarrhythmic effects, highlighting the potential of repurposing these antidiabetic drugs for heart failure treatment.