Transforming growth factor-β in myocardial disease

Nature Reviews Cardiology, Год журнала: 2022, Номер 19(7), С. 435 - 455

Опубликована: Янв. 4, 2022

Язык: Английский

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Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Язык: Английский

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Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 4004 - 4004

Опубликована: Фев. 16, 2023

Most chronic inflammatory illnesses include fibrosis as a pathogenic characteristic. Extracellular matrix (ECM) components build up in excess to cause or scarring. The fibrotic process finally results organ malfunction and death if it is severely progressive. Fibrosis affects nearly all tissues of the body. associated with inflammation, metabolic homeostasis, transforming growth factor-β1 (TGF-β1) signaling, where balance between oxidant antioxidant systems appears be key modulator managing these processes. Virtually every system, including lungs, heart, kidney, liver, can affected by fibrosis, which characterized an excessive accumulation connective tissue components. Organ frequently caused remodeling, also linked high morbidity mortality. Up 45% fatalities industrialized world are damage any organ. Long believed persistently progressing irreversible, has now been revealed very dynamic preclinical models clinical studies variety systems. pathways from and/or main topics this review. Furthermore, different organs their effects was discussed. Finally, we highlight many principal mechanisms fibrosis. These could considered promising targets for development potential therapies important human diseases.

Язык: Английский

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Phytochemistry and cardiovascular protective effects of Huang‐Qi (Astragali Radix)

Medicinal Research Reviews, Год журнала: 2021, Номер 41(4), С. 1999 - 2038

Опубликована: Янв. 19, 2021

Abstract Huang‐Qi (Astragali Radix) is an herbal tonic widely used in China and many other countries. It derived from the roots of Astragalus membranaceus A. var. mongholicus shows potent cardiovascular protective effects. In this article, we comprehensively reviewed 189 small molecules isolated two species discussed interspecies chemical differences. Moreover, summarized pharmacological activities mechanisms action its major bioactive compounds for treatment diseases. This review covers 171 references published between February 1983 March 2020.

Язык: Английский

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The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(5), С. 2617 - 2617

Опубликована: Фев. 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.

Язык: Английский

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Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 5, 2022

Diabetes is a systemic disease in which patients with diabetes may develop peripheral neuropathy of the lower extremities and vascular due to long-term continuous exposure high glucose. Delayed wound healing one major complications diabetes. Slow diabetic associated glucose toxicity. When condition deteriorates, patient needs be amputated, seriously affects quality life even endangers patient. In general, delayed lack chemokines, abnormal inflammatory response, angiogenesis epithelial formation, fibroblast dysfunction. The incidence several chronic debilitating conditions increasing diabetes, such as renal insufficiency, heart failure, hepatic insufficiency. Fibrosis an inappropriate deposition extracellular matrix (ECM) proteins. It common causing organ fibrotic mechanism fibroblasts involve direct activation permanent fibroblasts. also degeneration fibers after hyperglycemia stimulates immune cells, or organ-specific parenchymal cells. Numerous studies confirm that play essential role treating its complications. primary function construct reshape ECM. Nowadays, widespread use single-cell RNA sequencing (scRNA-seq), number have found become critical sentinel can detect not only regulation response but molecular pattern related injury. By exploring heterogeneity functional changes manuscript discusses used immunomodulatory factors refractory healing, providing new ideas for treatment healing.

Язык: Английский

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Inflammatory pathways in heart failure with preserved left ventricular ejection fraction: implications for future interventions

Cardiovascular Research, Год журнала: 2022, Номер 118(18), С. 3536 - 3555

Опубликована: Авг. 24, 2022

Abstract Many patients with symptoms and signs of heart failure have a left ventricular ejection fraction ≥50%, termed preserved (HFpEF). HFpEF is heterogeneous syndrome mainly affecting older people who many other cardiac non-cardiac conditions that often cast doubt on the origin symptoms, such as breathlessness, or signs, peripheral oedema, rendering them neither sensitive nor specific to diagnosis HFpEF. Currently, management directed at controlling treating comorbid hypertension, atrial fibrillation, anaemia, coronary artery disease. also characterized by persistent increase in inflammatory biomarkers. Inflammation may be key driver development progression its associated comorbidities. Detailed characterization pathways provide insights into pathophysiology guide future management. There growing interest novel therapies specifically designed target deregulated inflammation therapeutic areas, including cardiovascular However, large-scale clinical trials investigating effectiveness anti-inflammatory treatments are still lacking. In this manuscript, we review role possible implications for trials.

Язык: Английский

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Therapeutic delivery of microRNA-125a-5p oligonucleotides improves recovery from myocardial ischemia/reperfusion injury in mice and swine

Theranostics, Год журнала: 2023, Номер 13(2), С. 685 - 703

Опубликована: Янв. 1, 2023

Rationale: Clinical application of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) to alleviate myocardial ischemia/reperfusion (I/R) injury is compromised by the low cell engraftment rate uncontrolled exosomal content.As one their active ingredients, single-component microRNA therapy may have more inherent advantages.We sought find an ideal candidate determine whether it could reproduce cardioprotective effects MSCs MSC-Exos.Methods: Cardiac function remodeling in MSC, MSC-Exo, or oligonucleotide-treated mouse hearts were investigated after I/R injury.The oligonucleotides on cardiac (macrophages, cardiomyocytes, fibroblasts, endothelial cells) downstream mechanisms confirmed.Large animals also employed investigate safety therapy. Results:The results showed that microRNA-125a-5p (miR-125a-5p) enriched MSC-Exos, intramyocardial delivery modified (agomir) myocardium, as well exerted obvious cardioprotection increasing limiting adverse remodeling.In addition, miR-125a-5p agomir treatment increased M2 macrophage polarization, promoted angiogenesis, attenuated fibroblast proliferation activation, which subsequently contributed improvements cardiomyocyte apoptosis inflammation.Mechanistically, Klf13, Tgfbr1, Daam1 are considered targets for regulating macrophages, cells, respectively.Similar observed following a porcine model, with no increase risk arrhythmia hepatic, renal, toxicity.Conclusions: This targeted presents effective safe strategy repair.

Язык: Английский

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Cardiac fibroblasts and mechanosensation in heart development, health and disease

Nature Reviews Cardiology, Год журнала: 2022, Номер 20(5), С. 309 - 324

Опубликована: Ноя. 14, 2022

Язык: Английский

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Immunology of human fibrosis

Nature Immunology, Год журнала: 2023, Номер 24(9), С. 1423 - 1433

Опубликована: Июль 20, 2023

Язык: Английский

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