Mechanisms of liver fibrosis in metabolic syndrome DOI Creative Commons
Wajahat Z. Mehal

eGastroenterology, Journal Year: 2023, Volume and Issue: 1(1), P. e100015 - e100015

Published: Aug. 1, 2023

The understanding of the mechanisms liver fibrosis has been dominated by models in which chronic hepatocellular injury is initiating step as seen with viral infections. increased prevalence metabolic syndrome, and increases due to syndrome driven non-alcoholic steatohepatitis (NASH), made it a priority understand how this type similar to, different from, pure fibrosis. Both types have transformation hepatic stellate cell (HSC) into myofibroblast key step. In there little evidence that metabolite changes such high levels glucose free fatty acids are directly inducing HSC transdifferentiation, however, may lead reductions immunomodulatory hepatoprotective molecules lipoxins, resolvins Interleukin (IL)-22. Cells innate immune system known be important intermediaries between damage primarily producing cytokines transforming growth factor-β (TGF-β) platelet derived factor (PDGF). Resident infiltrating macrophages dominant cells, but others (dendritic neutrophils, natural killer T cells mucosal-associated invariant cells) also roles resolving CD8+ CD4+ adaptive identified greater profibrotic than previously realised hepatocyte death (auto-aggressive CD8+T) (TH17 CD4+T) cells. Finally, cellular networks present NASH being suggest once developed cell-to-cell communication myofibroblasts autocrine signalling followed cholangiocytes endothelial myofibroblast-hepatocyte, myofibroblast-macrophage having minor roles. Such information essential development antifibrotic strategies for stages

Language: Английский

Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis DOI
Santosh Kumar,

Qihua Duan,

Rongxue Wu

et al.

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 176, P. 113869 - 113869

Published: July 16, 2021

Language: Английский

Citations

231
Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus DOI Open Access
Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3587 - 3587

Published: March 25, 2022

There is a close relationship between diabetes mellitus and heart failure, an independent risk factor for failure. Diabetes failure are linked by not only the complication of ischemic disease, but also metabolic disorders such as glucose toxicity lipotoxicity based on insulin resistance. Cardiac dysfunction in absence coronary artery hypertension, valvular disease called diabetic cardiomyopathy. Diabetes-induced hyperglycemia hyperinsulinemia lead to capillary damage, myocardial fibrosis, hypertrophy with mitochondrial dysfunction. Lipotoxicity extensive fat deposits or lipid droplets observed cardiomyocytes. Furthermore, increased oxidative stress inflammation cause cardiac fibrosis hypertrophy. Treatment sodium cotransporter 2 (SGLT2) inhibitor currently one most effective treatments associated diabetes. However, treatment myocardium has yet been established, establishment needed future. This review provides overview patients clinical practice clinicians.

Language: Английский

Citations

153
Heart failure in diabetes DOI
Stanislovas S. Jankauskas, Urna Kansakar, Fahimeh Varzideh

et al.

Metabolism, Journal Year: 2021, Volume and Issue: 125, P. 154910 - 154910

Published: Oct. 8, 2021

Language: Английский

Citations

139
Inter-organ crosstalk during development and progression of type 2 diabetes mellitus DOI Open Access
Georgia Xourafa,

Melis Korbmacher,

Michael Roden

et al.

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 20(1), P. 27 - 49

Published: Oct. 16, 2023

Language: Английский

Citations

101
Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing DOI Creative Commons

Ye Liu,

Yiqiu Liu, Wenjie He

et al.

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

Published: Aug. 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.

Language: Английский

Citations

97
Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence DOI Open Access
Prisca K. Lin, George E. Davis

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2023, Volume and Issue: 43(9), P. 1599 - 1616

Published: July 6, 2023

Because of structural and cellular differences (ie, degrees matrix abundance cross-linking, mural cell density, adventitia), large medium-sized vessels, in comparison to capillaries, react a unique manner stimuli that induce vascular disease. A stereotypical injury response is ECM (extracellular matrix) remodeling occurs particularly larger vessels injurious stimuli, such as elevated angiotensin II, hyperlipidemia, hyperglycemia, genetic deficiencies, inflammatory infiltration, or exposure proinflammatory mediators. Even with substantial prolonged damage, large- arteries, persist, but become modified by (1) changes wall cellularity; (2) modifications the differentiation status endothelial cells, smooth muscle adventitial stem cells (each can activated); (3) infiltration various leukocyte types; (4) increased critical growth factors mediators; (5) marked ECM, remodels from homeostatic, prodifferentiation environment matrices instead promote tissue reparative responses. This latter presents previously hidden matricryptic sites bind integrins signal infiltrating leukocytes (in coordination other mediators) proliferate, invade, secrete ECM-degrading proteinases, deposit injury-induced (predisposing vessel fibrosis). In contrast, similar capillaries undergo regression responses (rarefaction). summary, we have described molecular events controlling major diseases well differential arteries versus key mediators inducing injury.

Language: Английский

Citations

45
Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities DOI Creative Commons
Izabela Tuleta, Nikolaos G. Frangogiannis

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 176, P. 113904 - 113904

Published: July 29, 2021

Language: Английский

Citations

88
Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction DOI Creative Commons
Chongxiang Xue, Keyu Chen, Zezheng Gao

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 30, 2023

Abstract Diabetic vascular complications (DVCs), including macro- and micro- angiopathy, account for a high percentage of mortality in patients with diabetes mellitus (DM). Endothelial dysfunction is the initial role step pathogenesis DVCs. Hyperglycemia lipid metabolism disorders contribute to endothelial via direct injury products, crosstalk between immunity inflammation, as well related interaction network. Although physiological phenotypic differences support their specified changes different targeted organs, there are still several common mechanisms underlying Also, inhibitors these may decrease incidence DVCs effectively. Thus, this review provide new insights into possible measures secondary prevention DM. And we discussed current limitations those present preventive research.

Language: Английский

Citations

38
NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways DOI Creative Commons
Linlin Meng, Yue Lu, Xinlu Wang

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(31)

Published: Aug. 2, 2023

Cardiac fibrosis plays a key role in the progression of diabetic cardiomyopathy (DCM). Previous studies demonstrated cardioprotective effects natriuretic peptides. However, peptide receptor C (NPRC) on cardiac DCM remains unknown. Here, we observed that myocardial NPRC expression was increased mice and patients with DCM.

Language: Английский

Citations

36
Vascular organoids: unveiling advantages, applications, challenges, and disease modelling strategies DOI Creative Commons
Hojjat Naderi‐Meshkin, Victoria A. Cornelius, Magdalini Eleftheriadou

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 10, 2023

Abstract Understanding mechanisms and manifestations of cardiovascular risk factors, including diabetes, on vascular cells such as endothelial cells, pericytes, smooth muscle remains elusive partly due to the lack appropriate disease models. Therefore, here we explore different aspects for development advanced 3D in vitro models that recapitulate human blood vessel complications using patient-derived induced pluripotent stem which retain epigenetic, transcriptomic, metabolic memory their patient-of-origin. In this review, highlight superiority organoids over conventional 2D cell culture systems research. We outline key benefits both health contexts discuss current challenges associated with organoid technology, providing potential solutions. Furthermore, diverse applications emphasize importance incorporating all relevant cellular components a model accurately pathophysiology. As specific example, present comprehensive overview diabetic vasculopathy, demonstrating how interplay types is critical successful modelling complex processes vitro. Finally, propose strategy creating an organ-specific vasculopathy model, serving valuable template other diseases by disease-specific stressors organotypic modifications. Graphical abstract

Language: Английский

Citations

31