Regulators of clonal hematopoiesis and physiological consequences of this condition DOI Open Access
Eunbee Park, Megan A. Evans, Kenneth Walsh

et al.

The Journal of Cardiovascular Aging, Journal Year: 2023, Volume and Issue: 4(3)

Published: Dec. 13, 2023

Clonal hematopoiesis (CH) is a prevalent condition that results from somatic mutations in hematopoietic stem cells. When these occur "driver" genes, they can potentially confer fitness advantages to the affected cells, leading clonal expansion. While most expansions of mutant cells are generally considered be asymptomatic since do not impact overall blood cell numbers, CH carriers face long-term risks all-cause mortality and age-associated diseases, including cardiovascular disease hematological malignancies. considerable research has focused on understanding association between less attention been given exploring regulatory factors contribute expansion driver gene clone. This review focuses environmental stressors inherited genetic risk context development. A better how development will facilitate mechanistic studies lead new therapeutic avenues treat individuals with this condition.

Language: Английский

Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages DOI Creative Commons
Anna Csiszár, Anna Ungvari, Roland Patai

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 5103 - 5132

Published: April 19, 2024

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They prevalent in the aging population, with multiple often being observed given individual. closely associated accelerated cognitive decline and increasingly recognized key contributors to pathogenesis vascular impairment dementia (VCID) Alzheimer's (AD). This review paper delves into hypothesis that atherosclerosis, age-related large disease, extends its influence microcirculation, thereby contributing development progression CSVD, specific focus on CMHs. We explore concept continuum, bridging macrovascular pathologies like atherosclerosis microvascular abnormalities characteristic CSVD. posit same risk factors precipitating vessels (i.e., atherogenesis), primarily oxidative stress inflammatory pathways, similarly instigate aging. Accelerated leads increased fragility, which turn predisposes formation The presence hypertension amyloid pathology further intensifies this process. comprehensively overview current body evidence supporting interconnected hypothesis. Our includes examination epidemiological data, provides insights prevalence impact context Furthermore, we shared mechanisms between aging, atherogenesis, particularly focusing how these intertwined processes contribute genesis By highlighting role pathophysiology CMHs, seeks enhance understanding CSVD links systemic disorders. aim is provide could inform future therapeutic approaches research directions realm neurovascular health.

Language: Английский

Citations

24

Challenges and advances in the management of inflammation in atherosclerosis DOI Creative Commons

Yiming Xing,

Xianhe Lin

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Atherosclerosis, traditionally considered a lipid-related disease, is now understood as chronic inflammatory condition with significant global health implications. This review aims to delve into the complex interactions among immune cells, cytokines, and cascade in atherosclerosis, shedding light on how these elements influence both initiation progression of disease. draws recent clinical research elucidate roles key macrophages, T endothelial clonal hematopoiesis atherosclerosis development. It focuses cells process contribute disease progression, particularly through inflammation-driven processes that lead plaque formation stabilization. Macrophages ingest oxidized low-density lipoprotein (oxLDL), which partially converts high-density (HDL) or accumulates lipid droplets, forming foam crucial for stability. Additionally, macrophages exhibit diverse phenotypes within plaques, pro-inflammatory types predominating others specializing debris clearance at rupture sites. The involvement CD4+ CD8+ promotes macrophage states, suppresses vascular smooth muscle cell proliferation, enhances instability. nuanced related atherosclerotic microenvironment are explored, revealing insights cellular molecular pathways fuel inflammation. also addresses advancements imaging biomarker technology enhance our understanding progression. Moreover, it points out limitations current treatment highlights potential emerging anti-inflammatory strategies, including trials agents such p38MAPK, tumor necrosis factor α (TNF-α), IL-1β, their preliminary outcomes, promising effects canakinumab, colchicine, IL-6R antagonists. explores cutting-edge interventions, efficacy preventing alleviating role nanotechnology delivering drugs more effectively safely.

Language: Английский

Citations

13

Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism DOI
Ariel H. Polizio, Lucila Marino, Kyung‐Duk Min

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 135(9), P. 933 - 950

Published: Sept. 5, 2024

BACKGROUND: Hypertension incidence increases with age and represents one of the most prevalent risk factors for cardiovascular disease. Clonal events in hematopoietic system resulting from somatic mutations driver genes are elderly individuals who lack overt hematologic disorders. This condition is referred to as age-related clonal hematopoiesis (CH), it a newly recognized factor It not known whether CH hypertension causally related and, if so, what mechanistic features. METHODS: A murine model adoptive bone marrow transplantation was employed examine interplay between Tet2 (ten-eleven translocation methylcytosine dioxygenase 2) hypertension. RESULTS: In this model, subpressor dose Ang II (angiotensin II) resulted elevated systolic diastolic blood pressure early 1 day after challenge. These conditions led expansion Tet2-deficient proinflammatory monocytes progenitor populations. deficiency promoted renal CCL5 (C-C motif ligand 5) chemokine expression macrophage infiltration into kidney. Consistent involvement, myeloid cells when mice were treated II. The −/− sodium retention, inflammasome activation, levels IL (interleukin)-1β IL-18. Analysis transporters indicated NCC (sodium-chloride symporter) NKCC2 (Na + -K -Cl − cotransporter activation at residues Thr53 Ser105, respectively. Administration NLRP3 (NLR family pyrin domain containing 3) inhibitor MCC950 reversed hypertensive state, transporter activation. CONCLUSIONS: Tet2-mediated sensitizes stimulus. Mechanistically, promotes due immune cell inflammasome, consequences on retention. data indicate that carriers TET2 could be development modulators useful treating patient population.

Language: Английский

Citations

10

Senoinflammation as the underlying mechanism of aging and its modulation by calorie restriction DOI
Sang Gyun Noh, Hyun‐Woo Kim, Seungwoo Kim

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102503 - 102503

Published: Sept. 1, 2024

Language: Английский

Citations

5

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL) DOI Creative Commons

Attila Kállai,

Zoltán Ungvári, Mónika Fekete

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Aging is a multifaceted process characterized by gradual decline in physiological function and increased susceptibility to range of chronic diseases. Among the molecular cellular mechanisms driving aging, genomic instability fundamental hallmark, contributing mutation load genetic heterogeneity within populations. This review explores role aging hematopoietic system, with particular focus on clonal hematopoiesis indeterminate potential (CHIP), monoclonal gammopathy undetermined significance (MGUS), B-cell lymphocytosis (MBL) as biomarkers. CHIP involves expansion stem cells somatic mutations. In contrast, MGUS presence plasma producing immunoglobulins, while MBL proliferation B cells. These conditions are prevalent population serve measurable indicators underlying instability. Studying these entities offers valuable insights into which mutations accumulate drive evolution providing deeper understanding how impacts tissue homeostasis. summary, system serves powerful model for investigating interplay between aging. Incorporating age-related hematological research, alongside other biomarkers such epigenetic clocks, can enhance precision predictive power biological age assessments. provide comprehensive view process, facilitating early detection diseases hopefully enabling personalized healthcare strategies.

Language: Английский

Citations

5

Clonal hematopoiesis: elements associated with clonal expansion and diseases DOI Open Access
Gangpyo Ryu, Youngil Koh, Siddhartha Jaiswal

et al.

Blood Research, Journal Year: 2025, Volume and Issue: 60(1)

Published: March 13, 2025

Abstract Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in 1960s, recent technological advances have revealed its complex nature widespread prevalence, affecting up to 84% individuals aged ≥ 70 years. The clinical significance CH extends beyond well-established role precursor hematological malignancies, encompassing association cardiovascular diseases, chronic kidney disease, other non-malignant disorders. This comprehensive review synthesizes current understanding CH, focusing on genetic molecular mechanisms, particularly roles commonly mutated genes such DNMT3A, TET2, ASXL1. We address emerging distinction between myeloid lymphoid their differential impacts disease progression, interplay inflammation. Special attention is given newly identified determinants clonal rates progression. also examines revolutionary concept passenger-approximated rate utility dynamics. Furthermore, we discuss therapeutic strategies targeting inflammatory pathways potential mitigating CH-associated complications. By integrating findings from genetic, molecular, studies, this provides framework systemic condition highlights promising directions interventions.

Language: Английский

Citations

0

Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis DOI Open Access
Shuanhu Li, Xin Zhou,

Qinchun Duan

et al.

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

Citations

0

Association between clonal hematopoiesis and periodontitis: a two-sample mendelian randomization study DOI Creative Commons
Feng Qiu, Wei Shao, Xuejun Qin

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 9, 2025

Language: Английский

Citations

0

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

Attila Kállai,

Anna Ungvari,

Dóra Csabán

et al.

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

Published: April 11, 2025

Language: Английский

Citations

0

Multiplex PCR for the Rapid Diagnosis of Myeloproliferative Neoplasms DOI

Laura Semenuk,

Alissa Palazzolo,

Kristen McCambridge

et al.

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0