Publications by authors named "Eleonora Cianflone"

Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease.

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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.

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  • 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.
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  • Cardiovascular calcification leads to calcium buildup in arterial walls, increasing stiffness and reducing elasticity, which raises the risk of heart-related illnesses.
  • Warfarin therapy has been linked to vascular calcification, but the specific mechanisms behind this are still not fully understood, though some pathways have been identified.
  • The review focuses on the latest research about how warfarin affects vascular calcification and considers the potential role of microRNA as biomarkers or targets in this process.
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  • 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.
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  • There is growing interest in the link between the immune and cardiovascular systems, highlighting their complex communication and regulation during cardiac injury and healing.
  • Macrophages are key immune cells involved in cardiac repair, with various subtypes affecting heart remodeling differently, and there are notable differences between the innate and adaptive immune systems in responding to cardiac damage.
  • This review aims to clarify the immune system's role, particularly the functions of macrophages in heart injury and potential new treatments for heart regeneration by modulating the immune response.
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  • 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.*
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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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  • Ischemic stroke remains a significant health issue despite advancements in diagnosis and treatment, contributing to high rates of illness and death.
  • Key challenges include identifying individuals at risk, timely diagnosis, recognizing different stroke types, evaluating treatment responses, and prognosis.
  • The article discusses how circular RNAs could serve as effective biomarkers to help address these challenges in stroke management through a systematic review of relevant studies.
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  • * 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.
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  • - 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.
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The outer layer of endothelial cells (ECs), consisting of the endothelial glycocalyx (eGC) and the cortex (CTX), provides a protective barrier against vascular diseases. Structural and functional impairments of their mechanical properties are recognized as hallmarks of endothelial dysfunction and can lead to cardiovascular events, such as acute myocardial infarction (AMI). This study investigated the effects of AMI on endothelial nanomechanics and function and the use of exogenous recombinant syndecan-1 (rSyn-1), a major component of the eGC, as recovering agent.

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  • 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.
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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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  • - Cardiac muscle damage leads to the loss of cardiomyocytes (CMs) and heart failure, a leading cause of death globally, highlighting the urgent need for therapies that promote heart regeneration.
  • - Current heart regeneration strategies focus on generating new functional CMs from existing cells, requiring a deep understanding of the processes involved in CM commitment and differentiation.
  • - The review emphasizes the role of microRNAs in CM differentiation, showcasing how both positive and negative regulatory mechanisms are crucial for effective cardiac regeneration in adults.
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  • 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.
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  • - Voltage-gated sodium channels (VGSCs) are crucial in heart myocytes for creating sodium currents that impact heart excitability, impulse conduction, and mechanical properties of the heart muscle.
  • - Research on mice with a specific gene deletion related to VGSC β1-subunits revealed increased sodium currents but compromised diastolic function and ventricular compliance, despite preserved systolic function.
  • - The study suggests that VGSC β1/β1B-subunits are important for regulating sodium influx and calcium cycling in heart cells, which influences how well the heart contracts and relaxes, ultimately affecting overall heart function.
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  • The research focuses on regenerating cardiac tissue after heart attacks, highlighting the need for effective solutions since myocardial tissue has limited self-repair abilities.
  • The study introduces glyceryl monooleate-based lyotropic liquid crystals (LLCs) as a promising new biomaterial for myocardial applications, showing advantages in biocompatibility and easy injection.
  • In vivo tests in mice demonstrated that LLCs did not disrupt heart function over 28 days and could biodegrade effectively, suggesting their potential for cardiac drug delivery.
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  • 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.
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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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