Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2023, Номер 43(9), С. 1599 - 1616

Опубликована: Июль 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.

Язык: Английский

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Advances in the treatment of atherosclerosis with ligand‐modified nanocarriers

Exploration, Год журнала: 2023, Номер 4(3)

Опубликована: Дек. 7, 2023

Abstract Atherosclerosis, a chronic disease associated with metabolism, poses significant risk to human well‐being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface‐modified nanoparticles holds potential deliver highly effective therapeutic outcomes. These can target and bind specific receptors that are abnormally over‐expressed in atherosclerotic conditions. This paper reviews recent research (2018–present) advances various ligand‐modified nanoparticle systems targeting by specifically signature molecules hope precise treatment at molecular level concludes discussion challenges prospects this field. The intention review is inspire novel concepts design advancement targeted nanomedicines tailored atherosclerosis.

Язык: Английский

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The Role of Cilostazol, a Phosphodiesterase-3 Inhibitor, in the Development of Atherosclerosis and Vascular Biology: A Review with Meta-Analysis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2593 - 2593

Опубликована: Фев. 23, 2024

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading global cause of mortality. Addressing this vital and pervasive condition requires a multifaceted approach, in which antiplatelet intervention plays pivotal role, together with antihypertensive, antidiabetic, lipid-lowering therapies. Among agents available currently, cilostazol, phosphodiesterase-3 inhibitor, offers spectrum pharmacological effects. These encompass vasodilation, impediment platelet activation aggregation, thrombosis inhibition, limb blood flow augmentation, lipid profile enhancement through triglyceride reduction high-density lipoprotein cholesterol elevation, suppression vascular smooth muscle cell proliferation. However, role cilostazol has not been clearly documented many guidelines for ASCVD. We comprehensively reviewed effects within randomized clinical trials that compared it to control or active involved individuals previous coronary artery stroke, well those no history such conditions. Our approach demonstrated administration effectively reduced adverse events, although there was less evidence regarding its impact on myocardial infarction. Most studies have consistently reported favorable reducing intermittent claudication enhancing ambulatory capacity patients peripheral arterial disease. Furthermore, shown promise mitigating restenosis following stent implantation acute syndrome. While research from more diverse regions is still needed, our findings shed light broader implications context atherosclerosis biology, particularly at high risk

Язык: Английский

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The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract BTB domain and CNC homolog 1 (BACH1) belongs to the family of basic leucine zipper proteins is expressed in most mammalian tissues. It can regulate its own expression play a role transcriptionally activating or inhibiting downstream target genes. has crucial various biological processes, such as oxidative stress, cell cycle, heme homeostasis, immune regulation. Recent research highlights BACH1's significant regulatory roles series conditions, including stem pluripotency maintenance differentiation, growth, senescence, apoptosis. BACH1 closely associated with cardiovascular diseases contributes angiogenesis, atherosclerosis, restenosis, pathological cardiac hypertrophy, myocardial infarction, ischemia/reperfusion (I/R) injury. promotes tumor proliferation metastasis by altering metabolism epithelial‐mesenchymal transition phenotype. Moreover, appears show an adverse neurodegenerative diseases, gastrointestinal disorders, leukemia, pulmonary fibrosis, skin diseases. Inhibiting may be beneficial for treating these This review summarizes mechanism different types proposing that precise targeted intervention provide new strategies human disease prevention treatment.

Язык: Английский

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Nanotechnology in development of next generation of stent and related medical devices: Current and future aspects

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Год журнала: 2024, Номер 16(2)

Опубликована: Март 1, 2024

Abstract Coronary stents have saved millions of lives in the last three decades by treating atherosclerosis especially, preventing plaque protrusion and subsequent aneurysms. They attenuate vascular SMC proliferation promote reconstruction endothelial bed to ensure superior revascularization. With evolution modern stent types, nanotechnology has become an integral part technology. Nanocoating nanosurface fabrication on metallic polymeric improved their drug loading capacity as well other mechanical, physico‐chemical, biological properties. Nanofeatures can mimic natural nanofeatures tissue control drug‐delivery. This review will highlight role addressing challenges coronary recent advancements field related medical devices. Different generations carrying nanoparticle‐based formulations like liposomes, lipid‐polymer hybrid NPs, micelles, dendrimers are discussed highlighting roles local delivery anti‐restenotic Drug nanoparticles Paclitaxel embedded metal a feature first‐generation drug‐eluting stents. Customized precision safe nanoparticle‐mediated genes or concerted transfer gene, drug, and/or bioactive molecules antibodies, gene mimics via nanofabricated Nanotechnology aid such therapies for successfully due its easy scale‐up possibilities. However, limitations this technology potential cytotoxic effects associated with nanoparticle that trigger hypersensitivity reactions also been review. article is categorized under: Implantable Materials Surgical Technologies > Tissue Repair Replacement Therapeutic Approaches Discovery Nanomedicine Cardiovascular Disease Emerging

Язык: Английский

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Elucidating VSMC phenotypic transition mechanisms to bridge insights into cardiovascular disease implications

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Май 13, 2024

Cardiovascular diseases (CVD) are the leading cause of death worldwide, despite advances in understanding cardiovascular health. Significant barriers still exist effectively preventing and managing these diseases. Vascular smooth muscle cells (VSMCs) crucial for maintaining vascular integrity can switch between contractile synthetic functions response to stimuli such as hypoxia inflammation. These transformations play a pivotal role progression diseases, facilitating modifications disease advancement. This article synthesizes current mechanisms signaling pathways regulating VSMC phenotypic transitions, highlighting their potential therapeutic targets interventions.

Язык: Английский

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Early Injury Landscape in Vein Harvest by Single-Cell and Spatial Transcriptomics

Circulation Research, Год журнала: 2024, Номер 135(1), С. 110 - 134

Опубликована: Май 29, 2024

Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. injury can occur during autogenous vein harvest preparation, as well after implantation into arterial system, leading development of intimal hyperplasia, stenosis, and, ultimately, failure. Although previous studies have identified maladaptive pathways that shortly implantation, specific signaling preparation are not defined may result a cumulative impact on We, therefore, aimed elucidate response conduit wall probing key driving with overarching goal identifying therapeutic targets for biologic intervention minimize these natural responses surgical injury.

Язык: Английский

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Hydrogen Sulfide and Oxygen Homeostasis in Atherosclerosis: A Systematic Review from Molecular Biology to Therapeutic Perspectives

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8376 - 8376

Опубликована: Май 6, 2023

Atherosclerosis is a complex pathological condition marked by the accumulation of lipids in arterial wall, leading to development plaques that can eventually rupture and cause thrombotic events. In recent years, hydrogen sulfide (H2S) has emerged as key mediator cardiovascular homeostasis, with potential therapeutic applications atherosclerosis. This systematic review highlights importance understanding interplay between H2S, oxygen atherosclerosis suggests targeting H2S signaling pathways may offer new avenues for treating preventing this condition. Oxygen homeostasis critical aspect health, disruption balance contribute progression Recent studies have demonstrated plays an important role maintaining regulating function oxygen-sensing enzymes transcription factors vascular cells. been shown modulate endothelial nitric oxide synthase (eNOS) activity, which tone delivery tissues. The comprehensive analysis current pave way future research strategies debilitating PROSPERO ID: 417150.

Язык: Английский

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Influence of DNA Methylation on Vascular Smooth Muscle Cell Phenotypic Switching

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3136 - 3136

Опубликована: Март 8, 2024

Vascular smooth muscle cells (VSMCs) are crucial components of the arterial wall, controlling blood flow and pressure by contracting relaxing artery walls. VSMCs can switch from a contractile to synthetic state, leading increased proliferation migratory potential. Epigenetic pathways, including DNA methylation, play role in regulating VSMC differentiation phenotypic flexibility. methylation involves attaching methyl group 5’ carbon cytosine base, which regulates gene expression interacting with transcription factors. Understanding key factors influencing plasticity may help identify new target molecules for development innovative drugs treat various vascular diseases. This review focuses on pathways VSMCs, summarizing mechanisms involved remodeling, significantly enhance our understanding related provide promising therapeutic approaches complex multifactorial

Язык: Английский

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The Effects of Statins, Ezetimibe, PCSK9-Inhibitors, Inclisiran, and Icosapent Ethyl on Platelet Function

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11739 - 11739

Опубликована: Июль 21, 2023

This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, manuscript provides an overview of effects major hypolipidemic drugs on function. Indeed, growing evidence supports view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, icosapent ethyl also act as antithrombotics. It is known platelets play a key role not only in acute phase coronary syndromes but early atherosclerotic plaque formation. The goal cholesterol-lowering therapy reduce cardiovascular events. direct are widely described literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results 22–23% reduction risk. Numerous studies have examined antithrombotic these platelets, endothelium, monocytes, smooth muscle cells, thus, potentially independent blood LDL-cholesterol reduction. We reviewed vitro vivo evaluating hypercholesterolemia, hypertriglyceridemia, First, we discussed statins modulating activation. Discontinuation statin was associated with increased events ox-LDL, P-selectin, aggregation. effect PCSK9-I (inhibitors proprotein convertase subtilisin/kexin type 9, involved degradation LDL receptors liver) statistically significant reactivity, calculated P2Y12 reaction units (PRU), first 14 days no difference at 30 compared placebo. Finally, patients REDUCE-IT study showed (an ester eicosapentaenoic acid reduces triglyceride synthesis improves clearance) resulted 25% ischemic death. However, date, there yet clear clinical may beneficial impact outcomes independently from LDL-C or triglycerides.

Язык: Английский

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