Signaling pathways and targeted therapy for myocardial infarction

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 10, 2022

Abstract Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and mortality. Whilst there long way to go for discovering ideal treatments, therapeutic strategies committed cardioprotection cardiac repair following ischemia are emerging. Evidence pathological characteristics in MI illustrates cell signaling pathways that participate survival, proliferation, apoptosis, autophagy cardiomyocytes, endothelial cells, fibroblasts, monocytes, stem cells. These include key players inflammation response, e.g., NLRP3/caspase-1 TLR4/MyD88/NF-κB; crucial mediators oxidative stress instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, Sonic hedgehog; controller fibrosis such as TGF-β/SMADs Wnt/β-catenin; main regulator angiogenesis, PI3K/Akt, MAPK, JAK/STAT, hedgehog, etc. Since play an important role administering process MI, aiming at targeting these aberrant improving manifestations indispensable promising. Hence, drug therapy, gene protein exosome therapy have been emerging known novel therapies. In this review, we summarize by regulating associated pathways, which contribute inhibiting cardiomyocytes death, attenuating inflammation, enhancing so re-functionalize damaged hearts.

Language: Английский

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The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1082 - 1082

Published: Jan. 16, 2024

With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms at play. Recently, numerous pro-inflammatory cytokines have been linked to several different CVDs, which are now often considered an adversely state. These most notably include interleukin-6 (IL-6),tumor necrosis factor (TNF)α, interleukin-1 (IL-1) family, amongst others. Not only does inflammation intricate complex interactions with processes such as oxidative stress calcium mishandling, but also plays role in balance between tissue repair destruction. In this regard, pre-clinical clinical evidence has clearly demonstrated involvement dynamic nature many heart conditions; however, utility findings so far remains unclear. Whether these can serve markers or risk predictors states act potential therapeutic targets, further extensive research needed fully network molecules encompass context disease. This review will highlight significant advances our understanding contributions including ischemic (atherosclerosis, thrombosis, acute myocardial infarction, ischemia-reperfusion injury), cardiac remodeling (hypertension, hypertrophy, fibrosis, apoptosis, failure), cardiomyopathies well ventricular arrhythmias atrial fibrillation. addition, article focused on discussing shortcomings both pathological aspects CVD still need be addressed by future studies.

Language: Английский

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Long COVID: a review and proposed visualization of the complexity of long COVID

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 20, 2023

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose visual description the complexity COVID its pathogenesis that can be used by researchers, clinicians, public health officials to guide global effort toward an improved understanding eventual mechanism-based provision care afflicted patients. The proposed visualization framework for should evidence-based, dynamic, modular, systems-level approach condition. Furthermore, further research such could establish strength relationships between pre-existing conditions (or risk factors), biological mechanisms, resulting clinical phenotypes outcomes COVID. Notwithstanding significant contribution disparities in access social determinants have on disease course long our model focuses primarily mechanisms. Accordingly, sets out scientific, clinical, efforts better understand abrogate burden imposed

Language: Английский

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DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 19, 2024

Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells other cardiac cell types remain unknown. Here, we identify fibroblasts as partners monocytes. We used combined transcriptomic data derived peripheral blood mononuclear HF patients, both without CHIP, tissue. demonstrate that inactivation DNMT3A macrophages intensifies increases fibrosis. amplifies release heparin-binding epidermal growth factor-like factor, thereby facilitating activation fibroblasts. These findings pathway CHIP-driver to initiation progression may also provide compelling basis for development innovative anti-fibrotic strategies.

Language: Английский

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Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 22, 2024

Abstract Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of derived from pluripotent stem cells are often limited due to their immaturity lack functionality. Therefore, in this study, we establish a perfusable culture system based on vivo-like heart microenvironments improve tissue fabrication. The integrated platform microfluidic chip three-dimensional extracellular matrix enhances development structural functional maturation. These comprised cardiovascular lineage cells, cardiomyocytes fibroblasts induced as well vascular endothelial cells. resultant macroscale exhibit improved efficacy testing (small molecules with levels arrhythmia risk), modeling (Long QT Syndrome fibrosis), therapy (myocardial infarction treatment). our can serve highly effective tissue-engineering provide versatile applications.

Language: Английский

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Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2023, Volume and Issue: 24(5), P. 901 - 919

Published: June 26, 2023

Abstract Obesity epidemic reached the dimensions of a real global health crisis with more than one billion people worldwide living obesity. Multiple obesity-related mechanisms cause structural, functional, humoral, and hemodynamic alterations cardiovascular (CV) deleterious effects. A correct assessment risk in obesity is critical for reducing mortality preserving quality life. The identification status remains difficult as recent evidence suggest that different phenotypes exist, each associated degrees CV risk. Diagnosis cannot depend only on anthropometric parameters but should include precise metabolic status. Recently, World Heart Federation provided an action plan management mortality, stressing instauration comprehensive structured programs encompassing multidisciplinary teams. In this review we aim at providing updated summary regarding phenotypes, their specific effects differences clinical management.

Language: Английский

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Emerging Antiarrhythmic Drugs for Atrial Fibrillation

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4096 - 4096

Published: April 7, 2022

Atrial fibrillation (AF), the most common cardiac arrhythmia worldwide, is driven by complex mechanisms that differ between subgroups of patients. This complexity apparent from different forms in which AF presents itself (post-operative, paroxysmal and persistent), each with heterogeneous patterns variable progression. Our current understanding responsible for initiation, maintenance progression has increased significantly recent years. Nevertheless, antiarrhythmic drugs management have not been developed based on underlying none currently used were specifically to target AF. With knowledge AF, new opportunities developing more effective safer therapies are emerging. In this review, we provide an overview potential novel approaches focusing both development agents possibility repurposing already marketed drugs. addition, discuss opportunity targeting some key players involved mechanisms, such as ryanodine receptor type-2 (RyR2) channels atrial-selective K+-currents (IK2P ISK) therapy. highlight components inflammatory signaling (e.g., NLRP3-inflammasome) upstream fibroblast function prevent structural remodeling Finally, critically appraise emerging drug principles future directions development, well their improving management.

Language: Английский

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Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1801 - 1801

Published: Jan. 16, 2023

Myofibroblasts escape apoptosis and proliferate abnormally under pathological conditions, especially fibrosis; they synthesize secrete a large amount of extracellular matrix (ECM), such as α-SMA collagen, which leads to the distortion organ parenchyma structure, an imbalance in collagen deposition degradation, replacement parenchymal cells by fibrous connective tissues. Fibroblast myofibroblast transition (FMT) is considered be main source myofibroblasts. Therefore, it crucial explore influencing factors regulating process FMT for prevention, treatment, diagnosis FMT-related diseases. In recent years, non-coding RNAs, including microRNA, long circular have attracted extensive attention from scientists due their powerful regulatory functions, been found play vital role FMT. this review, we summarized ncRNAs regulate during fibrosis that mainly regulated signaling pathways, TGF-β/Smad, MAPK/P38/ERK/JNK, PI3K/AKT, WNT/β-catenin. Furthermore, expression downstream transcription can promoted or inhibited, indicating potential new therapeutic target

Language: Английский

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Progress and prospect of nanotechnology for cardiac fibrosis treatment

Deleted Journal, Journal Year: 2023, Volume and Issue: 1(4)

Published: Sept. 5, 2023

Abstract Cardiac fibrosis is the excessive accumulation of extracellular matrix components in heart, leading to reduced cardiac functionality and heart failure. This review provides an overview therapeutic applications nanotechnology for treatment fibrosis. We first delve into fundamental pathophysiology fibrosis, highlighting key molecular players, including Matrix Metalloproteinases, Transforming Growth Factor‐beta, several growth factors, cytokines, signaling molecules. Each target presents a unique opportunity develop targeted nano‐therapies. then focus on recent advancements how nanoparticles can be engineered deliver drugs or genes. These advanced delivery approaches have shown significant potential inhibit fibrosis‐promoting thereby mitigating fibrotic response potentially reversing disease progression. In addition, we discuss challenges associated with developing translating nanotechnology‐based drug systems, ensuring biocompatibility, safety, regulatory compliance. highlights bridge gap between lab research clinical practice treating

Language: Английский

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Cardiomyocyte engineering: The meeting point of transcription factors, signaling networks, metabolism and function

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 12, 2025

Abstract Direct cardiac reprogramming or transdifferentiation is a relatively new and promising area in regenerative therapy, cardiovascular disease modeling, drug discovery. Effective of fibroblasts limited by their plasticity, that is, ability to reprogram, depends on solving several levels tasks: inducing cardiomyocyte‐like cells obtaining functionally metabolically mature cardiomyocytes. Currently, addition the use more classical approaches such as overexpression exogenous transcription factors, activation endogenous factors via controlled nucleases, CRISPR, represents another interesting way obtain Therefore, special attention given potential synthetic biology, particular CRISPR system, for targeted conversion only certain subpopulations into However, cardiomyocytes remains challenge despite range recently developed approaches. In this review, we summarized current knowledge function diversity human alternative cell sources vitro cardiomyocyte models. We examined detail initiate cardiomyogenic interactions. Additionally, critically analyzed strategies used metabolic physiological maturation induced

Language: Английский

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