Coronary Artery Calcification: Current Concepts and Clinical Implications

Circulation, Journal Year: 2024, Volume and Issue: 149(3), P. 251 - 266

Published: Jan. 16, 2024

Coronary artery calcification (CAC) accompanies the development of advanced atherosclerosis. Its role in atherosclerosis holds great interest because presence and burden coronary provide direct evidence extent disease; furthermore, CAC predicts future events independently concomitant conventional cardiovascular risk factors to a greater than any other noninvasive biomarker this disease. Nevertheless, relationship between susceptibility plaque provoke thrombotic event remains incompletely understood. This review summarizes current understanding literature on CAC. It outlines pathophysiology reviews laboratory, histopathological, genetic studies, as well imaging findings, characterize different types elucidate their implications. Some patterns such microcalcification portend increased rupture may improve prognosis assessment noninvasively. However, contemporary computed tomography cannot assess early microcalcification. Limited spatial resolution blooming artifacts hinder estimation degree stenosis. Technical advances photon counting detectors combination with nuclear approaches (eg, NaF imaging) promise performance cardiac tomography. These innovations speed achieving ultimate goal providing noninvasively specific clinically actionable information.

Language: Английский

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SCAI Expert Consensus Statement on the Management of Calcified Coronary Lesions

Journal of the Society for Cardiovascular Angiography & Interventions, Journal Year: 2024, Volume and Issue: 3(2), P. 101259 - 101259

Published: Jan. 31, 2024

The prevalence of calcification in obstructive coronary artery disease is on the rise. Percutaneous intervention these calcified lesions associated with increased short-term and long-term risks. To optimize percutaneous results, there an expanding array treatment modalities geared toward calcium modification prior to stent implantation. Society for Cardiovascular Angiography Interventions, herein, puts forth expert consensus document regarding methods identify types lesions, a central algorithm help guide use various strategies, tips when using each modality, look at future studies trials treating this challenging lesion subset.

Language: Английский

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Screening of immune-related secretory proteins linking chronic kidney disease with calcific aortic valve disease based on comprehensive bioinformatics analysis and machine learning

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 1, 2023

Chronic kidney disease (CKD) is one of the most significant cardiovascular risk factors, playing vital roles in various diseases such as calcific aortic valve (CAVD). We aim to explore CKD-associated genes potentially involving CAVD pathogenesis, and discover candidate biomarkers for diagnosis CKD with CAVD.Three CAVD, CKD-PBMC CKD-Kidney datasets expression profiles were obtained from GEO database. Firstly, detect key secretory proteins, differentially expressed analysis WGCNA carried out. Protein-protein interaction (PPI), functional enrichment cMAP analyses employed reveal CKD-related pathogenic underlying mechanisms well potential drugs treatment. Then, machine learning algorithms including LASSO regression random forest adopted screening constructing diagnostic nomogram predicting CAVD. Moreover, ROC curve, calibration curve decision applied evaluate performance nomogram. Finally, CIBERSORT algorithm was used immune cell infiltration CAVD.The integrated dataset identified 124 by intersecting differential analyses. Totally 983 proteins screened CKD-PBMC/Kidney datasets. PPI two modules containing 76 nodes, regarded which mostly enriched inflammatory regulation analysis. The exposed metyrapone a more drug 17 overlapped between hub chosen developing ideal through learning. Furthermore, SLPI/MMP9 patterns confirmed our external cohort could serve novel models distinguishing results uncovered dysregulation significantly associated invasive cells.We revealed inflammatory-immune pathways developed SLPI/MMP9-based nomogram, offered insights into future serum-based therapeutic intervention

Language: Английский

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Age-related loss of Notch3 underlies brain vascular contractility deficiencies, glymphatic dysfunction, and neurodegeneration in mice

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 134(2)

Published: Nov. 28, 2023

Vascular aging impacts multiple organ systems, including the brain, where it can lead to vascular dementia. However, a concrete understanding of how specifically affects brain vasculature, along with molecular read-outs, remain vastly incomplete. Here we demonstrate that is associated marked decline in Notch3 signaling both murine and human vessels. To clarify consequences loss used single-cell transcriptomics uncovered inactivation alters regulation calcium, contractile function, promotes notable increase extracellular matrix. These alterations adversely impact reactivity, manifesting as dilation, tortuosity, microaneurysms, decreased cerebral blood flow, observed by MRI. Combined, these impairments hinder glymphatic flow result buildup glycosaminoglycans within parenchyma. Remarkably, this phenomenon mirrors key pathological feature found brains CADASIL patients – hereditary dementia NOTCH3 missense mutations. Additionally, RNA sequencing neuronal compartment null mice has unveiled patterns reminiscent those neurodegenerative diseases. findings offer direct evidence age-related deficiencies trigger progressive subsequently affecting culminating neurodegeneration.

Language: Английский

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Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 275 - 275

Published: Feb. 25, 2024

Calcification is a process of accumulation calcium in tissues and deposition salts by the crystallization PO43− ionized (Ca2+). It crucial development bones teeth. However, pathological calcification can occur almost any soft tissue organism. The better studied vascular calcification, where accumulate intima or medial layer aortic valves, it associated with higher mortality cardiovascular events, including myocardial infarction, stroke, peripheral artery disease (PAD), diabetes chronic kidney (CKD), among others. involves an intricate interplay different cellular components, endothelial cells (ECs), smooth muscle (VSMCs), fibroblasts, pericytes, concurrent activation several signaling pathways, calcium, Wnt, BMP/Smad, Notch, regulation molecular mediators, growth factors (GFs), osteogenic matrix vesicles (MVs). In present review, we aim to explore players, biomarkers, clinical treatment strategies provide current comprehensive overview topic.

Language: Английский

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The Indissociable Triad: Vascular Impairment, Muscle Atrophy, and Cognitive Decline

Published: Aug. 12, 2024

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating mass reduction seen in sarcopenia the neuronal functions characteristic neurodegeneration. Our limited understanding intricate relationships within this hinders accurate diagnosis effective treatment strategies. This review ana-lyzes interrelated mechanisms contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, impaired nutrient delivery. aim is understand common pathways involved suggest comprehensive therapeutic approaches. dysfunctions hinder circulation transportation nutrients, resulting sar-copenia characterized by atrophy weakness. dysfunction have negative physical function quality life. Neurodegenerative diseases exhibit comparable pathophysiological affect motor functions. Preventive approaches encompass lifestyle adjustments, addressing oxidative in-flammation, integrated therapies improving muscular well-being. Better links can refine strategies yield better patient out-comes. study emphasizes complex interplay between dysfunction, de-generation, decline, highlighting necessity for multidisciplinary ap-proaches. Advances domain promise improved diagnostic accuracy, more thera-peutic options, enhanced preventive measures, all contributing higher life elderly population.

Language: Английский

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Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification

Circulation, Journal Year: 2024, Volume and Issue: 149(22), P. 1752 - 1769

Published: Feb. 13, 2024

BACKGROUND: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, an actively regulated process that involves complex mechanisms. calcification associated with increased cardiovascular adverse events. The role 4-hydroxynonenal (4-HNE), most abundant stable product lipid peroxidation, has been poorly investigated. METHODS: Serum was collected from patients chronic kidney disease controls, levels 4-HNE 8-iso-prostaglandin F2α were measured. Sections coronary atherosclerotic plaques donors immunostained to analyze 4-HNE. A total 658 artery who received computed tomography angiography recruited relationship between rs671 mutation aldehyde dehydrogenase 2 ( ALDH2 ). knockout -/ - ) mice, cell–specific transgenic their controls used establish models. Primary mouse aortic cells human exposed medium containing β-glycerophosphate CaCl investigate cell underlying molecular RESULTS: Elevated observed serum model mice detected calcified sections immunostaining. or accelerated development whereas overexpression activation prevented cells. In disease, gene developed more severe calcification. promoted both vitro. level Runx2 (runt-related transcription factor-2), effect on promoting ablated when knocked down. Mutation at lysine 176 reduced its carbonylation eliminated 4-HNE–induced upregulation Runx2. CONCLUSIONS: Our results suggest increases stabilization directly carbonylating K176 site promotes might be a potential target for treatment

Language: Английский

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A new mechanism of arterial calcification in diabetes: interaction between H3K18 lactylation and CHI3L1

Clinical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation lactate the microenvironment can promote VSMC calcification diabetes, although specific mechanism remains to be fully elucidated. In this study, we explored characteristics lactylation diabetic arterial and underlying molecular mechanism. We found that high-glucose calcified VSMC, overall level was significantly increased. Mass spectrometry analysis revealed significant upregulation H3 histone lactylation. After site-specific point-mutation at K18 simulate delactylation modification, reduced. Through a combination H3K18la ChIP-seq, RNA-seq, ChIP-qPCR experiments, confirmed upregulate CHI3L1. CHI3L1 knockout alleviated osteogenic phenotype transformation mouse calcification. RNA-seq downstream signaling showed activates IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition IL-13Ra2 reduced conclude environment, site undergoes modification VSMCs, upregulating CHI3L1, which turn regulates pathway, ultimately exacerbating Our study elucidates epigenetic by promotes

Language: Английский

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The Implications of Aging on Vascular Health

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11188 - 11188

Published: Oct. 17, 2024

Vascular aging encompasses structural and functional changes in the vasculature, significantly contributing to cardiovascular diseases, which are leading cause of death globally. The incidence prevalence these diseases increase with age, most morbidity mortality attributed myocardial infarction stroke. Diagnosing intervening vascular while understanding mechanisms behind age-induced phenotypic pathophysiological alterations offers potential for delaying preventing an population. This review delves into various aspects by examining age-related arterial health at cellular level, including endothelial dysfunction, senescence, smooth muscle cell transdifferentiation, as well stiffness wall thickness diameter. We also explore aging-related perivascular adipose tissue deposition, collateralization, calcification, providing insights physiological pathological implications. Overall, induces that augment system’s susceptibility disease, even absence traditional risk factors, such hypertension, diabetes, obesity, smoking. modifications phenotype molecular homeostasis vulnerability vasculature alterations, thereby accelerating risk. Increasing our is crucial success or diseases. Non-invasive techniques, measuring carotid intima-media thickness, pulse wave velocity, flow-mediated dilation, detecting calcifications, can be used early detection aging. Targeting specific mechanisms, senescence enhancing angiogenesis, holds promise innovative therapeutic approaches.

Language: Английский

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Atherosclerosis Calcification: Focus on Lipoproteins

Metabolites, Journal Year: 2023, Volume and Issue: 13(3), P. 457 - 457

Published: March 21, 2023

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids in vessel wall, leading to formation an atheroma and eventually development vascular calcification (VC). Lipoproteins play central role atherosclerosis VC. Both low- very low-density lipoproteins (LDL VLDL) lipoprotein (a) (Lp(a)) stimulate, while high-density (HDL) reduce Apolipoproteins, protein component lipoproteins, influence VC multiple ways. Apolipoprotein AI (apoAI), main HDL, has anti-calcific properties, apoB apoCIII, components LDL VLDL, respectively, promote The also related their metabolism modifications. Oxidized (OxLDL) are more pro-calcific than native LDL. Oxidation converts HDL from anti- pro-calcific. Additionally, enzymes such as autotaxin (ATX) proprotein convertase subtilisin/kexin type 9 (PCSK9), involved metabolism, have stimulatory In summary, better understanding mechanisms which apolipoproteins contribute will be crucial effective preventive therapeutic strategies for its associated cardiovascular disease.

Language: Английский

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