Signaling pathways and targeted therapy for myocardial infarction

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Март 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.

Язык: Английский

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The Hippo signalling pathway and its implications in human health and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Ноя. 8, 2022

Abstract As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in regulation of numerous biological processes. Thus, substantial efforts have been made to understand upstream signals that influence activity pathway, as well its physiological functions, such cell proliferation and differentiation, organ growth, embryogenesis, tissue regeneration/wound healing. However, dysregulation can cause variety diseases, including cancer, eye cardiac pulmonary renal hepatic immune dysfunction. Therefore, therapeutic strategies target dysregulated components might be promising approaches for treatment wide spectrum diseases. Here, we review key critical functions controlled by pathway. Additionally, diseases associated with alterations potential therapies targeting will discussed.

Язык: Английский

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Control of stem cell renewal and fate by YAP and TAZ

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(12), С. 895 - 911

Опубликована: Авг. 25, 2023

Язык: Английский

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siRNA Delivery against Myocardial Ischemia Reperfusion Injury Mediated by Reversibly Camouflaged Biomimetic Nanocomplexes

Advanced Materials, Год журнала: 2023, Номер 35(23)

Опубликована: Март 13, 2023

siRNA-mediated management of myocardial ischemia reperfusion (IR) injury is greatly hampered by the inefficient enrichment and cardiomyocyte transfection. Herein, nanocomplexes (NCs) reversibly camouflaged with a platelet-macrophage hybrid membrane (HM) are developed to efficiently deliver Sav1 siRNA (siSav1) into cardiomyocytes, suppressing Hippo pathway inducing regeneration. The biomimetic BSPC@HM NCs consist cationic nanocore assembled from membrane-penetrating helical polypeptide (P-Ben) siSav1, charge-reversal intermediate layer poly(l-lysine)-cis-aconitic acid (PC), an outer shell HM. Due HM-mediated inflammation homing microthrombus targeting, intravenously injected can accumulate in IR-injured myocardium, where acidic inflammatory microenvironment triggers charge reversal PC shed off both HM layers allow penetration exposed P-Ben/siSav1 cardiomyocytes. In rats pigs, remarkably downregulates promotes myocardium regeneration, suppresses apoptosis, recovers cardiac functions. This study reports bioinspired strategy overcome multiple systemic barriers against delivery, holds profound potential for gene therapy injuries.

Язык: Английский

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MOF-derived bimetallic nanozyme to catalyze ROS scavenging for protection of myocardial injury

Theranostics, Год журнала: 2023, Номер 13(8), С. 2721 - 2733

Опубликована: Янв. 1, 2023

Rationale: Myocardial injury triggers intense oxidative stress, inflammatory response, and cytokine release, which are essential for myocardial repair remodeling.Excess reactive oxygen species (ROS) scavenging inflammation elimination have long been considered to reverse injuries.However, the efficacy of traditional treatments (antioxidant, anti-inflammatory drugs natural enzymes) is still poor due their intrinsic defects such as unfavorable pharmacokinetics bioavailability, low biological stability, potential side effects.Nanozyme represents a candidate effectively modulate redox homeostasis treatment ROS related diseases.Methods: We develop an integrated bimetallic nanozyme derived from metal-organic framework (MOF) eliminate alleviate inflammation.The (Cu-TCPP-Mn) synthesized by embedding manganese copper into porphyrin followed sonication, could mimic cascade activities superoxide dismutase (SOD) catalase (CAT) transform radicals hydrogen peroxide, catalysis peroxide water.Enzyme kinetic analysis oxygen-production velocities were performed evaluate enzymatic Cu-TCPP-Mn.We also established infarction (MI) ischemia-reperfusion (I/R) animal models verify anti-inflammation effect Cu-TCPP-Mn.Results: As demonstrated analysis, Cu-TCPP-Mn possesses good performance in both SOD-and CAT-like achieve synergistic provide protection injury.In MI I/R models, this promising reliable technology protect heart tissue stress inflammation-induced injury, enables function recover otherwise severe damage.Conclusions: This research provides facile applicable method MOF nanozyme, alternative injuries.

Язык: Английский

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The Hippo signaling pathway in development and regeneration

Cell Reports, Год журнала: 2024, Номер 43(3), С. 113926 - 113926

Опубликована: Март 1, 2024

The Hippo signaling pathway is a central growth control mechanism in multicellular organisms. By integrating diverse mechanical, biochemical, and stress cues, the orchestrates proliferation, survival, differentiation, mechanics of cells, which turn regulate organ development, homeostasis, regeneration. A deep understanding regulation function therefore holds great promise for developing novel therapeutics regenerative medicine. Here, we provide updates on molecular organization mammalian network, review regulatory signals functional outputs pathway, discuss roles development

Язык: Английский

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YAP induces a neonatal-like pro-renewal niche in the adult heart

Nature Cardiovascular Research, Год журнала: 2024, Номер 3(3), С. 283 - 300

Опубликована: Фев. 14, 2024

Язык: Английский

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Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction

npj Regenerative Medicine, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 22, 2025

Myocardial infarction (MI) causes the loss of millions cardiomyocytes, and current treatments do not address this root issue. New therapies focus on stimulating cardiomyocyte division in adult heart, inspired by regenerative capacities lower vertebrates neonatal mice. This review explores strategies for heart regeneration, offers insights into proliferation, evaluates vivo models, discusses integrating vitro human cardiac models to advance regeneration research.

Язык: Английский

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Molecular Regulation of Cardiomyocyte Maturation

Current Cardiology Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Янв. 21, 2025

Язык: Английский

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Guidelines for in vivo mouse models of myocardial infarction

AJP Heart and Circulatory Physiology, Год журнала: 2021, Номер 321(6), С. H1056 - H1073

Опубликована: Окт. 9, 2021

Despite significant improvements in reperfusion strategies, acute coronary syndromes all too often culminate a myocardial infarction (MI). The consequent MI can, turn, lead to remodeling of the left ventricle (LV), development LV dysfunction, and ultimately progression heart failure (HF). Accordingly, an improved understanding underlying mechanisms HF is necessary. One common approach examine pathology with murine models that recapitulate components clinical context syndrome subsequent MI. We evaluated different approaches used produce mouse identified opportunities consolidate methods, recognizing reperfused nonreperfused yield responses. overall goal compiling this consensus statement unify best practices regarding improve interpretation allow comparative examination across studies laboratories. These guidelines will help establish rigor reproducibility provide increased potential for translation. Listen another corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-in-vivo-mouse-models-of-myocardial-infarction/ .

Язык: Английский

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