Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology DOI Open Access
Aman Singh,

Kriti Bhatt,

Hien C. Nguyen

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6180 - 6180

Published: June 4, 2024

Under different pathophysiological conditions, endothelial cells lose phenotype and gain mesenchymal cell-like via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, expression of cell-specific markers such CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, vascular-endothelial cadherin α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, collagens. EndMT is induced by numerous pathways triggered modulated multiple often redundant mechanisms in context-dependent manner depending on status cell. plays an essential role embryonic development, particularly atrioventricular valve development; however, also implicated pathogenesis several genetically determined acquired diseases, including malignant, cardiovascular, inflammatory, fibrotic disorders. Among cardiovascular aberrant reported atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, cardiac fibrosis. Accordingly, understanding behind cause and/or effect to eventually target appears be promising strategy for treating EndMT-associated diseases. However, this approach limited lack precise functional pathways, causes effects, robust animal models human data about Here, we review various

Language: Английский

Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies DOI Creative Commons
Xiumei Wu, Mengyun Xu,

M. Geng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 27, 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.

Language: Английский

Citations

103
Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification DOI Open Access
Nadia R. Sutton, Rajeev Malhotra, Cynthia St. Hilaire

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2022, Volume and Issue: 43(1), P. 15 - 29

Published: Nov. 22, 2022

Cardiovascular disease is the most common cause of death worldwide, especially beyond age 65 years, with vast majority morbidity and mortality due to myocardial infarction stroke. Vascular pathology stems from a combination genetic risk, environmental factors, biologic changes associated aging. The pathogenesis underlying development vascular aging, calcification in particular, still not fully understood. Accumulating data suggests that likely compounded by epigenetic modifications, including diabetes chronic kidney disease, plasticity smooth muscle cells acquire an osteogenic phenotype are major determinants age-associated calcification. Understanding molecular mechanisms modifiable risk factors regulating may inspire strategies promote healthy This article summarizes current knowledge concepts emphasis on

Language: Английский

Citations

74
Vascular Inflammatory Diseases and Endothelial Phenotypes DOI Creative Commons
Jenita Immanuel, Sanguk Yun

Cells, Journal Year: 2023, Volume and Issue: 12(12), P. 1640 - 1640

Published: June 15, 2023

The physiological functions of endothelial cells control vascular tone, permeability, inflammation, and angiogenesis, which significantly help to maintain a healthy system. Several cardiovascular diseases are characterized by cell activation or dysfunction triggered external stimuli such as disturbed flow, hypoxia, growth factors, cytokines in response high levels low-density lipoprotein cholesterol, hypertension, diabetes, aging, drugs, smoking. Increasing evidence suggests that uncontrolled proinflammatory signaling further alteration phenotypes barrier disruption, increased mesenchymal transition (EndMT), metabolic reprogramming induce diseases, multiple studies focusing on finding the pathways mechanisms involved it. This review highlights main their effects function. In order provide rational direction for future research, we also compiled most recent data regarding impact potential targets impede pathogenic process.

Language: Английский

Citations

46
Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease DOI Creative Commons
Ignacio Fernando Hall,

Franceska Kishta,

Yang Xu

et al.

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(3), P. 223 - 236

Published: Feb. 1, 2024

Abstract Endothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as barrier, sensing circulating factors intrinsic/extrinsic signals. ECs have capacity to undergo endothelial-to-mesenchymal transition (EndMT), complex differentiation process with key roles both during embryonic development adulthood. EndMT can contribute EC activation dysfunctional alterations associated maladaptive tissue responses human disease. During EndMT, progressively changes leading expression mesenchymal markers while repressing lineage-specific traits. This phenotypic functional switch is considered largely exist continuum, being characterized gradation transitioning stages. In this report, we discuss plasticity potential reversibility hypothesis that different EndMT-derived cell populations may disease progression or resolution. addition, review advancements field, current technical challenges, well therapeutic options opportunities context cardiovascular biology.

Language: Английский

Citations

30
ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT DOI Creative Commons

Mengdie Dong,

Yunjia Zhang,

Minghong Chen

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 3027 - 3048

Published: March 12, 2024

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis increased in the endothelium atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated lactate, can regulate gene expression and participate disease regulation. However, whether histone lactylation involved atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced increasing lactate-dependent H3 lysine 18 (H3K18la) vitro vivo, as well atherosclerotic patients' arteries. Mechanistically, chaperone ASF1A was first identified cofactor P300, which precisely regulated enrichment H3K18la at promoter SNAI1, thereby activating SNAI1 transcription promoting EndMT. We found deletion inhibited EndMT improved endothelial dysfunction. Functional analysis based on ApoeKOAsf1aECKO mice model confirmed involvement endothelium-specific deficiency alleviated development. Inhibition pharmacologic inhibition advanced PROTAC attenuated H3K18la, transcription, This study illustrates precise crosstalk between metabolism epigenetics via P300/ASF1A molecular complex during atherogenesis, provides emerging therapies for

Language: Английский

Citations

18
Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies DOI Creative Commons

Nanlin You,

Guohao Liu, Mengchen Yu

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The modification of endothelial cells (ECs) biological function under pathogenic conditions leads to the expression mesenchymal stromal (MSCs) markers, defined as endothelial-to-mesenchymal transition (EndMT). Invisible in onset and slow progression, atherosclerosis (AS) is a potential contributor various atherosclerotic cardiovascular diseases (ASCVD). By triggering AS, EndMT, "initiator" induces progression ASCVD such coronary heart disease (CHD) ischemic cerebrovascular (ICD), with serious clinical complications myocardial infarction (MI) stroke. In-depth research pathomechanisms EndMT identification targeted therapeutic strategies hold considerable value for prevention treatment ASCVD-associated delayed EndMT. Although previous studies have progressively unraveled complexity its pathogenicity triggered by alterations vascular microenvironmental factors, systematic descriptions most recent roles strategies, their future directions are scarce.

Language: Английский

Citations

2
A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis DOI Creative Commons
Yaw Asare,

Guangyao Yan,

Christina Schlegl

et al.

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association its proinflammatory properties, we examined mechanisms whereby HDAC9 regulates vascular inflammation. bound mediated deacetylation NLRP3 NACHT LRR domains leading to inflammasome activation lytic cell death. Targeted deletion critical CRE mice increased Hdac9 expression myeloid cells exacerbate inflammasome-dependent chronic In human carotid endarterectomy samples, was associated with atheroprogression clinical plaque instability. Incorporation TMP195, class IIa HDAC inhibitor, into lipoprotein-based nanoparticles target site myeloid-driven inflammation stabilized atherosclerotic plaques, implying lower rupture events. Our findings link atherogenic provide paradigm anti-inflammatory therapeutics atherosclerosis.

Language: Английский

Citations

2
Mouse models of atherosclerosis in translational research DOI Creative Commons
Iqra Ilyas, Peter J. Little, Zhiping Liu

et al.

Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(11), P. 920 - 939

Published: July 25, 2022

Language: Английский

Citations

63
Endothelial to Mesenchymal Transition in Health and Disease DOI Creative Commons
Yang Xu, Jason C. Kovacic

Annual Review of Physiology, Journal Year: 2022, Volume and Issue: 85(1), P. 245 - 267

Published: Oct. 21, 2022

The endothelium is one of the largest organ systems in body, and data continue to emerge regarding importance endothelial cell (EC) dysfunction vascular aging a range cardiovascular diseases (CVDs). Over last two decades as process intimately related EC dysfunction, an increasing number studies have also implicated mesenchymal transition (EndMT) potentially disease-causal pathobiologic that involved multitude differing CVDs. However, EndMT physiologic processes (e.g., cardiac development), transient may contribute regeneration certain contexts. Given involves major alteration EC-specific molecular program, it contributes CVD pathobiology, clinical translation opportunities are significant, but further translational research needed see these realized.

Language: Английский

Citations

58
Role of Histone Post-Translational Modifications in Inflammatory Diseases DOI Creative Commons
Yingying Lin, Ting Qiu, Guifeng Wei

et al.

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

Published: Feb. 24, 2022

Inflammation is a defensive reaction for external stimuli to the human body and generally accompanied by immune responses, which associated with multiple diseases such as atherosclerosis, type 2 diabetes, Alzheimer’s disease, psoriasis, asthma, chronic lung diseases, inflammatory bowel virus-associated diseases. Epigenetic mechanisms have been demonstrated play key role in regulation of inflammation. Common epigenetic regulations are DNA methylation, histone modifications, non-coding RNA expression; among these, modifications embrace various post-modifications including acetylation, phosphorylation, ubiquitination, ADP ribosylation. This review focuses on significant progression providing potential target clinical therapy inflammation-associated

Language: Английский

Citations

55