Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities DOI
Ingo Hilgendorf, Stefan Frantz, Nikolaos G. Frangogiannis

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 134(12), P. 1718 - 1751

Published: June 6, 2024

The adult mammalian heart has limited endogenous regenerative capacity and heals through the activation of inflammatory fibrogenic cascades that ultimately result in formation a scar. After infarction, massive cardiomyocyte death releases broad range damage-associated molecular patterns initiate both myocardial systemic responses. TLRs (toll-like receptors) NLRs (NOD-like recognize (DAMPs) transduce downstream proinflammatory signals, leading to upregulation cytokines (such as interleukin-1, TNF-α [tumor necrosis factor-α], interleukin-6) chemokines CCL2 [CC chemokine ligand 2]) recruitment neutrophils, monocytes, lymphocytes. Expansion diversification cardiac macrophages infarcted play major role clearance infarct from dead cells subsequent stimulation reparative pathways. Efferocytosis triggers induction release anti-inflammatory mediators restrain reaction set stage for fibroblasts vascular cells. Growth factor–mediated pathways, neurohumoral cascades, matricellular proteins deposited provisional matrix stimulate fibroblast proliferation myofibroblast conversion. Deposition well-organized collagen-based extracellular network protects catastrophic rupture attenuates ventricular dilation. Scar maturation requires signals inhibit activity prevent excessive fibrosis. Moreover, mature scar, neovessels acquire mural cell coat contributes stabilization microvascular network. Excessive, prolonged, or dysregulated accentuate adverse remodeling dysfunction. leukocytes can contribute arrhythmogenesis. Inflammatory pathways may be promising therapeutic targets attenuate failure progression arrhythmia generation patients surviving infarction.

Language: Английский

Diabetic fibrosis DOI Creative Commons
Izabela Tuleta, Nikolaos G. Frangogiannis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2020, Volume and Issue: 1867(4), P. 166044 - 166044

Published: Dec. 28, 2020

Language: Английский

Citations

140
Properties and Functions of Fibroblasts and Myofibroblasts in Myocardial Infarction DOI Creative Commons
Harikrishnan Venugopal, Anis Hanna, Claudio Humeres

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(9), P. 1386 - 1386

Published: April 20, 2022

The adult mammalian heart contains abundant interstitial and perivascular fibroblasts that expand following injury play a reparative role but also contribute to maladaptive fibrotic remodeling. Following myocardial infarction, cardiac undergo dynamic phenotypic transitions, contributing the regulation of inflammatory, reparative, angiogenic responses. This review manuscript discusses mechanisms regulation, roles fate in infarcted heart. During inflammatory phase infarct healing, release alarmins by necrotic cells promotes pro-inflammatory matrix-degrading fibroblast phenotype may leukocyte recruitment. clearance dead matrix debris from stimulates anti-inflammatory pathways activates transforming growth factor (TGF)-β cascades, resulting conversion α-smooth muscle actin (α-SMA)-expressing myofibroblasts. Activated myofibroblasts secrete large amounts proteins form collagen-based scar protects ventricle catastrophic complications, such as rupture. Moreover, repair stimulating angiogenesis. maturation, disassemble α-SMA+ stress fibers convert specialized serve maintenance. prolonged activation border zone remote remodeling myocardium adverse pathogenesis failure. In addition their plasticity, exhibit remarkable heterogeneity. Subsets with distinct profiles be responsible for wide range functions populations hearts.

Language: Английский

Citations

137
Transforming growth factor–β1 in regulatory T cell biology DOI
J. Moreau, Maria Velegraki,

Chelsea Bolyard

et al.

Science Immunology, Journal Year: 2022, Volume and Issue: 7(69)

Published: March 18, 2022

Transforming growth factor-β1 (TGF-β1) is inextricably linked to regulatory T cell (Treg) biology. However, precisely untangling the role for TGF-β1 in Treg differentiation and function complicated by pleiotropic context-dependent activity of this cytokine multifaceted biology Tregs. Among CD4+ cells, Tregs are major producers latent uniquely able activate via expression surface docking receptor glycoprotein A repetitions predominant (GARP) αv integrins. Although a preponderance evidence indicates no essential roles Treg-derived immunosuppression, signaling crucial development thymus periphery. Furthermore, active instructs other subsets, including TH17 cells. Here, we will review discuss knowledge gaps, future research, TGF-β1/Treg axis context cancer immunotherapy fibrosis.

Language: Английский

Citations

134
Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches DOI Open Access
Innokenty A. Savin, Marina A. Zenkova,

Aleksandra V. Sen’kova

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14959 - 14959

Published: Nov. 29, 2022

Pulmonary fibrosis is a chronic progressive lung disease that steadily leads to architecture disruption and respiratory failure. The development of pulmonary mostly the result previous acute inflammation, caused by wide variety etiological factors, not resolved over time causing deposition fibrotic tissue in lungs. Despite long history study good coverage problem scientific literature, effective therapeutic approaches for treatment are currently lacking. Thus, molecular mechanisms underlying transition from inflammation fibrosis, search new markers promising targets prevent development, remain highly relevant tasks. This review focuses on etiology, pathogenesis, morphological characteristics outcomes as precursor fibrosis; pathomorphological changes lungs during development; known key players signaling pathways mediating well most common vivo models these processes. Moreover, prognostic injury severity approved potential suppressing discussed.

Language: Английский

Citations

125
The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress DOI Open Access
Kazuaki Maruyama, Kyoko Imanaka‐Yoshida

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2617 - 2617

Published: Feb. 27, 2022

Fibrosis is defined as the excessive deposition of extracellular matrix (ECM) proteins in interstitium. It an essential pathological response to chronic inflammation. ECM protein initially protective and critical for wound healing tissue regeneration. However, cardiac remodeling continuous damage with subsequent results a distorted organ architecture significantly impacts function. In this review, we summarized discussed histologic features fibrosis signaling factors that control it. We evaluated origin characteristic markers fibroblasts. also lymphatic vessels, which have become more important recent years improve fibrosis.

Language: Английский

Citations

119
Frozen shoulder DOI
Neal L. Millar, Adam Meakins, Filip Struyf

et al.

Nature Reviews Disease Primers, Journal Year: 2022, Volume and Issue: 8(1)

Published: Sept. 8, 2022

Language: Английский

Citations

114
Therapeutic targets for cardiac fibrosis: from old school to next-gen DOI Creative Commons
Joshua G. Travers, Charles A. Tharp, Marcello Rubino

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(5)

Published: Feb. 28, 2022

Cardiovascular diseases remain the leading cause of death worldwide, with pathological fibrotic remodeling mediated by activated cardiac myofibroblasts representing a unifying theme across etiologies. Despite profound contributions myocardial fibrosis to dysfunction and heart failure, there currently exist limited clinical interventions that effectively target fibroblast its role in tissue deposition. Exploration novel strategies designed mitigate or reverse myofibroblast activation will likely yield powerful therapeutic approaches for treatment multiple heart, including failure preserved reduced ejection fraction, acute coronary syndrome, cardiovascular disease linked type 2 diabetes. In this Review, we provide an overview classical regulators highlight emerging, next-generation epigenetic regulatory targets have potential revolutionize expanding patient population.

Language: Английский

Citations

111
Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy DOI Creative Commons

Meng-ling Peng,

Yu Fu,

Chu-wen Wu

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 15, 2022

Diabetes is a chronic metabolic disease that increasing in prevalence and causes many complications. Diabetic cardiomyopathy (DCM) complication of diabetes associated with high mortality, but it not well defined. Nevertheless, generally accepted DCM refers to clinical occurs patients involves ventricular dysfunction, the absence other cardiovascular diseases, such as coronary atherosclerotic heart disease, hypertension, or valvular disease. However, currently uncertain whether pathogenesis directly attributable dysfunction secondary diabetic microangiopathy. Oxidative stress (OS) considered be key component its pathogenesis. The production reactive oxygen species (ROS) cardiomyocytes vicious circle, resulting further ROS, mitochondrial DNA damage, lipid peroxidation, post-translational modification proteins, inflammation, cardiac hypertrophy fibrosis, ultimately leading cell death dysfunction. ROS have been shown affect various signaling pathways involved development DCM. For instance, OS disorders by affecting regulation PPARα, AMPK/mTOR, SIRT3/FOXO3a. Furthermore, participates inflammation mediated NF-κB pathway, NLRP3 inflammasome, TLR4 pathway. also promotes TGF-β-, Rho-ROCK-, Notch-mediated remodeling, calcium homeostasis, which impairs ATP overproduction. In this review, we summarize link DCM, intention identifying appropriate targets new antioxidant therapies for

Language: Английский

Citations

83
Regulatory Mechanism of M1/M2 Macrophage Polarization in the Development of Autoimmune Diseases DOI Creative Commons
Yuan Peng,

Mengxian Zhou,

Yang Hong

et al.

Mediators of Inflammation, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 20

Published: June 8, 2023

Macrophages are innate immune cells in the organism and can be found almost tissues organs. They highly plastic heterogeneous participate response, thereby playing a crucial role maintaining homeostasis of body. It is well known that undifferentiated macrophages polarize into classically activated (M1 macrophages) alternatively (M2 under different microenvironmental conditions. The directions macrophage polarization regulated by series factors, including interferon, lipopolysaccharide, interleukin, noncoding RNAs. To elucidate various autoimmune diseases, we searched literature on with PubMed database. Search terms as follows: macrophages, polarization, signaling pathways, RNA, inflammation, systemic lupus erythematosus, rheumatoid arthritis, nephritis, Sjogren’s syndrome, Guillain-Barré multiple sclerosis. In present study, summarize common diseases. addition, also features recent advances particular focus immunotherapeutic potential diseases potentially effective therapeutic targets.

Language: Английский

Citations

70
Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions DOI Creative Commons

Jin-Ling Huo,

Qi Feng, Shaokang Pan

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 21, 2023

Abstract Diabetic cardiomyopathy (DCM) mainly refers to myocardial metabolic dysfunction caused by high glucose, and hyperglycemia is an independent risk factor for cardiac function in the absence of coronary atherosclerosis hypertension. DCM, which a severe complication diabetes, has become leading cause heart failure diabetic patients. The initial symptoms are inconspicuous, patients gradually exhibit left ventricular eventually develop total failure, brings great challenge early diagnosis DCM. To date, underlying pathological mechanisms DCM complicated have not been fully elucidated. Although there therapeutic strategies available treatment focused on controlling blood glucose lipids, lack effective drugs targeting injury. Thus, large percentage with inevitably failure. Given neglected symptoms, intricate cellular molecular mechanisms, drugs, it necessary explore diagnostic biomarkers, further understand signaling pathways involved pathogenesis summarize current strategies, new targeted interventions.

Language: Английский

Citations

65