Inflammation in atherosclerotic cardiovascular disease: From diagnosis to treatment

European Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Targeting inflammation offers a unique possibility to address residual cardiovascular risk in almost two thirds of all patients with prevalent atherosclerotic disease (ASCVD). However, despite FDA approval and the ESC 2024 Guidelines for Management Chronic Coronary Syndrome recommendations implement low-dose colchicine (0.5 mg daily) secondary prevention ASCVD inflammatory risk, its clinical adoption is still limited. In this regard, simple screening elevated high-sensitive C-reactive protein (hsCRP) on routine basis might help recognize low-grade as an important therapeutic target. Within present review, we first provide recently published epidemiologic evidence that hsCRP at least strong predictor future events traditional lipoproteins. Furthermore, summarize our recent knowledge currently available strategies modulate process critically discuss open issues regarding benefit therapy acute coronary setting or stroke prevention. addition, also briefly touch upon some specific safety related long-term use colchicine. Finally, next diagnostic frontiers targeting such detection vascular/coronary by pericoronary fat attenuation ziltivekimab, human monoclonal antibody interleukin-6. Thus, integration interventions aimed lowering burden combination aggressive lipid-modifying may hold potential further reduce substantial ASCVD.

Language: Английский

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Deciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 671 - 671

Published: Jan. 14, 2025

Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (1011-1012) of new generated daily a healthy young human adult are origin. Therapeutically, HSCs contributed to over 1.5 million transplants (HCTs) globally, making this the most successful regenerative therapy date. We will commence review by briefly highlighting selected key achievements (from 1868 end 20th century) that accomplishment. Much our knowledge hematopoiesis is based on small animal models that, despite their importance, do not always recapitulate hematopoiesis. Given this, we critically progress challenges faced identifying tracing lineage differentiation trajectories, referring murine studies needed. Moving forward given dynamic can readily adjust variety stressors, then discuss recent research advances contributing understanding (i) which HSPCs maintain hematopoiesis, (ii) where these located, (iii) mechanisms come into play when homeostatic switches stress-induced or emergency

Language: Английский

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Innovative Atherosclerosis Models: Advancing Pathophysiology and Translational Research

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Atherosclerosis (AS) is a chronic inflammatory condition influenced by glucose and lipid disorders, oxidative stress, thrombosis, reflecting the complexity of its pathological process. The development accurate experimental models that simulate human AS essential for understanding initiation progression. This review summarizes current research analyzes their specific application scenarios. We discuss tissue-engineered blood vessels (TEBVs) vessels-on-a-chip (VoCs), which leverage tissue engineering precise microenvironmental control to construct in vitro closely resemble structure function AS. Isolated vessel segments from live animals provide valuable tool investigating due physiological similarity, controllability, reproducibility. further outlines construction animal through high-fat diets gene-editing techniques, highlighting how immune-inflammatory responses, mechanical arterial injury, hemodynamic changes accelerate model development. comprehensive analysis highlights potential revolutionize theranostic applications clinical translational research, paving way more personalized effective treatments near future.

Language: Английский

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Clonal hematopoiesis, cardiovascular disease and cancer treatment-induced cardiotoxicity

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3252 - 3252

Published: April 1, 2025

Atherosclerosis, a chronic inflammatory disease characterized by lipid accumulation and immune cell infiltration, is linked to plaque formation cardiovascular events. While traditionally associated with metabolism endothelial dysfunction, recent research highlights the roles of autophagy clonal hematopoiesis (CH) in its pathogenesis. Autophagy, cellular process crucial for degrading damaged components, regulates macrophage homeostasis inflammation, both which are pivotal atherosclerosis. In macrophages, influences metabolism, cytokine regulation, oxidative stress, helping prevent instability. Defective exacerbates impairs cholesterol efflux, accelerates progression. Additionally, autophagic processes cells smooth muscle further contribute atherosclerotic pathology. Recent studies also emphasize interplay between CH, wherein somatic mutations genes like TET2, JAK2, DNMT3A drive expansion enhance responses plaques. These modify function, intensifying environment accelerating Chaperone-mediated (CMA), selective form autophagy, plays critical role regulating inflammation pro-inflammatory cytokines oxidized low-density lipoprotein (ox-LDL). Impaired CMA activity leads these substrates, activating NLRP3 inflammasome worsening inflammation. Preclinical suggest that pharmacologically may mitigate atherosclerosis animal models, reduced instability increases This review importance regulation focusing on formation, contributions CH. Building upon current advances, we propose hypothesis programmed death, intrinsic axis modulates fundamental functions playing complex development Understanding mechanisms offers potential therapeutic strategies targeting reduce burden disease.

Language: Английский

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Clonal hematopoiesis of indeterminate potential (CHIP) in cerebromicrovascular aging: implications for vascular contributions to cognitive impairment and dementia (VCID)

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

Published: April 11, 2025

Language: Английский

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Global trends and research status in clonal hematopoiesis: a bibliometric analysis of the last 10 years

Published: April 28, 2025

Objective: Clonal hematopoiesis (CH) refers to the clonal expansion of hematopoietic stem cells caused by somatic mutations. CH is commonly observed in elderly individuals and closely associated with myeloid malignancies as well various non-malignant diseases. This study aims explore research trends hotspots using bibliometric analysis. Methods: Relevant studies were retrieved from Web Science Core Collection database based on predefined inclusion criteria. Bibliometric analysis visualization conducted VOSviewer, CiteSpace, R software. Results: A total 851 included. From 2014 2024, annual number publications showed a consistent upward trend. The United States was identified leading country this field, contributing 53.7% publications. Harvard Medical School Benjamin L Ebert recognized most influential institution author, respectively. Blood prolific journal, highest citation H-index. Research CH-related gene mutations their association risk acute leukemia currently extensively studied area, while cardiovascular diseases inflammation have emerged recent hotspots. Conclusion: first systematically analyze related methods. Our reveals overall landscape identifies contributors including countries, institutions, authors, journals. Moreover, we identify emerging key areas, highlighting potential avenues for exploration innovation within field CH.

Language: Английский

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The emergence of clonal hematopoiesis as a disease determinant

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(19)

Published: Sept. 30, 2024

Language: Английский

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PCSK9 Inhibitors: Focus on Evolocumab and Its Impact on Atherosclerosis Progression

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1581 - 1581

Published: Nov. 25, 2024

This paper investigates the therapeutic use of PCSK9 inhibitors, particularly Evolocumab, as monoclonal antibodies for treatment atherosclerosis based on recent literature reviews. is an outstanding example a breakthrough in medical science, with advancements understanding its biological function driving substantial progress treatment. Atherosclerotic cardiovascular disease (ASCVD) leading global cause mortality, imposing financial burdens healthcare systems. Elevated low-density lipoprotein cholesterol (LDL-C), modifiable risk factor, plays pivotal role development ASCVD. Emerging treatments such inhibitors are now being introduced to combat this issue, goal reducing ASCVD by directly targeting LDL-C levels. discovery highlighted potential inhibit PCSK9, thereby enhancing receptor activity. led Alirocumab and Evolocumab which typically reduce levels approximately 50%. research underscores importance treating ASCVD, drawing evidence from various randomized controlled trials FOURIER, ODYSSEY OUTCOMES, VESALIUS-CV. These have also shown that effective safe several disorders. therefore useful patients who do not reach their target when highest doses statins or very high cannot tolerate at all.

Language: Английский

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Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation

Thrombosis Research, Journal Year: 2024, Volume and Issue: 245, P. 109236 - 109236

Published: Dec. 6, 2024

Language: Английский

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