Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease DOI Creative Commons
Qi Pang, Peiwen Wang, Yajing Pan

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(3)

Published: March 30, 2022

Irisin protects the cardiovascular system against vascular diseases. However, its role in chronic kidney disease (CKD) -associated calcification (VC) and underlying mechanisms remain unclear. In present study, we investigated potential link among Irisin, pyroptosis, VC under CKD conditions. During mouse smooth muscle cell (VSMC) induced by β-glycerophosphate (β-GP), pyroptosis level was increased, as evidenced upregulated expression of pyroptosis-related proteins (cleaved CASP1, GSDMD-N, IL1B) pyroptotic death (increased numbers PI-positive cells LDH release). Reducing levels a CASP1 inhibitor remarkably decreased calcium deposition β-GP-treated VSMCs. Further experiments revealed that pathway activated excessive reactive oxygen species (ROS) production subsequent NLR family pyrin domain containing 3 (NLRP3) inflammasome activation calcified Importantly, effectively inhibited β-GP-induced VSMCs vitro mice aortic rings ex vivo. Overexpression Nlrp3 attenuated suppressive effect on VSMC calcification. addition, could induce autophagy restore autophagic flux Adding 3-methyladenine or chloroquine inhibitory ROS production, NLRP3 activation, Finally, our vivo study showed treatment promoted autophagy, downregulated thereby suppressed medial tissues adenine-induced mice. Together, findings for first time demonstrated protected via inducing inhibiting CKD, might serve an effective therapeutic agent CKD-associated VC.

Language: Английский

Vascular smooth muscle cells in atherosclerosis DOI
Gemma Basatemur, Helle F. Jørgensen, Murray C.H. Clarke

et al.

Nature Reviews Cardiology, Journal Year: 2019, Volume and Issue: 16(12), P. 727 - 744

Published: June 26, 2019

Language: Английский

Citations

842
Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases DOI Creative Commons
Theodore S. Kapellos, Lorenzo Bonaguro, Ioanna D. Gemünd

et al.

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Aug. 30, 2019

Human monocytes are divided in three major populations; classical (CD14+CD16-), non-classical (CD14dimCD16+), and intermediate (CD14+CD16+). Each of these subsets is distinguished from each other by the expression distinct surface markers their functions homeostasis disease. In this review, we discuss most up-to-date phenotypic classification human that has been greatly aided application novel single-cell transcriptomic mass cytometry technologies. Furthermore, shed light on role plastic immune cells already recognized emerging chronic diseases, such as obesity, atherosclerosis, obstructive pulmonary disease, lung fibrosis, cancer, Alzheimer's Our aim to provide an insight into contribution progression diseases highlight candidacy potential therapeutic cell targets.

Language: Английский

Citations

697
Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide DOI Creative Commons
Hai‐Jian Sun, Zhiyuan Wu, Xiaowei Nie

et al.

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 21, 2020

Endothelial cells are important constituents of blood vessels that play critical roles in cardiovascular homeostasis by regulating fluidity and fibrinolysis, vascular tone, angiogenesis, monocyte/leukocyte adhesion, platelet aggregation. The normal endothelium is taken as a gatekeeper health, whereas abnormality major contributor to plethora ailments, such atherosclerosis, aging, hypertension, obesity, diabetes. dysfunction characterized imbalanced vasodilation vasoconstriction, elevated reactive oxygen species (ROS), proinflammatory factors, well deficiency nitric oxide (NO) bioavailability. occurrence endothelial disrupts the barrier permeability part inflammatory response development diseases. As such, abrogation cell activation/inflammation clinical relevance. Recently, hydrogen sulfide (H2S), an entry gasotransmitter, exerts diverse biological effects through acting on various targeted signaling pathways. Within system, formation H2S detected smooth muscle cells, cardiomyocytes. Disrupted bioavailability postulated be new indicator for inflammation its associated dysfunction. In this review, we will summarize recent advances about homeostasis, especially under pathological conditions, discuss putative therapeutic applications inflammation-associated disorders.

Language: Английский

Citations

440
Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis DOI Creative Commons
Gabriel F. Alencar, Katherine Owsiany, Santosh Karnewar

et al.

Circulation, Journal Year: 2020, Volume and Issue: 142(21), P. 2045 - 2059

Published: July 17, 2020

Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause death. However, we have limited understanding identity, origin, function many cells that make up late-stage lesions, as well mechanisms by which they control plaque stability.

Language: Английский

Citations

297
Vascular smooth muscle cells in atherosclerosis: time for a re-assessment DOI
Mandy O. J. Grootaert, Martin R. Bennett

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 117(11), P. 2326 - 2339

Published: Feb. 5, 2021

Vascular smooth muscle cells (VSMCs) are key participants in both early and late-stage atherosclerosis. VSMCs invade the atherosclerotic lesion from media, expanding lesions, but also forming a protective fibrous cap rich extracellular matrix to cover 'necrotic' core. Hence, have been viewed as plaque-stabilizing, decreased VSMC plaque content-often measured by expression of contractile markers-associated with increased vulnerability. However, emergence lineage-tracing transcriptomic studies has demonstrated that comprise much larger proportion plaques than originally thought, demonstrate multiple different phenotypes vivo, roles might be detrimental. down-regulate markers during atherosclerosis whilst adopting alternative phenotypes, including macrophage-like, foam cell-like, osteochondrogenic-like, myofibroblast-like, mesenchymal stem cell-like. phenotypic switching can studied tissue culture, now deep-core region, markedly affects formation stability. In this review, we describe their presumed cellular paracrine functions, regulatory mechanisms control plasticity, impact on atherogenesis

Language: Английский

Citations

289
Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation DOI Open Access
Ploingarm Petsophonsakul, Malgorzata Furmanik, Rachael O. Forsythe

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2019, Volume and Issue: 39(7), P. 1351 - 1368

Published: May 30, 2019

Aortic aneurysm is a vascular disease whereby the ECM (extracellular matrix) of blood vessel degenerates, leading to dilation and eventually wall rupture. Recently, it was shown that calcification involved in both initiation progression aneurysms. Changes aortic structure lead formation are actively mediated by smooth muscle cells. Vascular cells healthy termed contractile as they maintain tone remain quiescent. However, pathological conditions can dedifferentiate into synthetic phenotype, secrete extracellular vesicles, proliferate, migrate repair injury. This process called phenotypic switching often first step pathology. Additionally, synthesize VKDPs (vitamin K-dependent proteins), which inhibition calcification. The metabolism these proteins known be disrupted pathologies. In this review, we summarize current literature on cell relation aneurysm. Moreover, address role vitamin K Visual Overview— An online visual overview available for article.

Language: Английский

Citations

281
Randall’s plaque and calcium oxalate stone formation: role for immunity and inflammation DOI
Saeed R. Khan, Benjamin K. Canales, Paul R. Dominguez‐Gutierrez

et al.

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(6), P. 417 - 433

Published: Jan. 29, 2021

Language: Английский

Citations

259
Role of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation DOI Creative Commons
V. A. Sorokin, Keeran Vickneson, Theo Kofidis

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 26, 2020

The pathobiology of atherosclerotic disease requires further elucidation to discover new approaches address its high morbidity and mortality. To date, over 17 million cardiovascular-related deaths have been reported annually, despite a multitude surgical nonsurgical interventions advances in medical therapy. Existing strategies prevent progression mainly focus on management risk factors, such as hypercholesterolemia. Even with optimum current therapy, recurrent cardiovascular events are not uncommon patients atherosclerosis, their incidence can reach 10–15% per year. Although treatments targeting inflammation under investigation continue evolve, clinical breakthroughs possible only if we deepen our understanding vessel wall pathobiology. Vascular smooth muscle cells (VSMCs) one the most abundant walls emerged key players progression. New technologies, including situ hybridization proximity ligation assays, vivo cell fate tracing CreER T2 -loxP system single-cell sequencing technology spatial resolution, broaden complex biology these intriguing cells. Our knowledge contractile synthetic VSMC phenotype switching has expanded include macrophage-like even osteoblast-like phenotypes. An increasing body data suggests that VSMCs remarkable plasticity play role cell-to-cell crosstalk endothelial immune during process inflammation. These sense, interact influence behavior other cellular components wall. It is now more obvious ability perform nonprofessional phagocytic functions phenomena maintaining inflammatory state senescent condition actively interacting different competent

Language: Английский

Citations

226
Repression of the antiporter SLC7A11/glutathione/glutathione peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification DOI
Yuanzhi Ye, An Chen, Li Li

et al.

Kidney International, Journal Year: 2022, Volume and Issue: 102(6), P. 1259 - 1275

Published: Sept. 3, 2022

Language: Английский

Citations

205
Biomarkers of aging DOI Open Access

Hainan Bao,

Jiani Cao, Mengting Chen

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

Citations

203