Heart Rhythm, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Circulation Research, Год журнала: 2023, Номер 132(11), С. 1505 - 1520
Опубликована: Май 25, 2023
The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) and colchicine trials suggest an important role of inflammasomes their major product IL-1β (interleukin 1β) in human atherosclerotic cardiovascular disease. Moreover, studies mouse models indicate a causal atherosclerosis. However, recent have led to more granular view the Studies hyperlipidemic that prominent activation NLRP3 inflammasome requires second hit such as defective cholesterol efflux, DNA repair, clonal hematopoiesis or diabetes. Similarly humans some mutations promoting increase coronary artery disease risk part by activation. Recent mice point wider AIM2 (absent melanoma 2) including forms These developments precision medicine approach which treatments targeting might be best employed clinical settings involving increased
Язык: Английский
Процитировано
45
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Янв. 19, 2024
Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells other cardiac cell types remain unknown. Here, we identify fibroblasts as partners monocytes. We used combined transcriptomic data derived peripheral blood mononuclear HF patients, both without CHIP, tissue. demonstrate that inactivation DNMT3A macrophages intensifies increases fibrosis. amplifies release heparin-binding epidermal growth factor-like factor, thereby facilitating activation fibroblasts. These findings pathway CHIP-driver to initiation progression may also provide compelling basis for development innovative anti-fibrotic strategies.
Язык: Английский
Процитировано
31
Circulation, Год журнала: 2023, Номер 148(15), С. 1165 - 1178
Опубликована: Сен. 8, 2023
Clonal hematopoiesis (CH), which results from an array of nonmalignant driver gene mutations, can lead to altered immune cell function and chronic disease, has been associated with worse outcomes in patients heart failure (HF) reduced ejection fraction. However, the role CH prognosis HF preserved fraction (HFpEF) understudied. This study aimed characterize HFpEF elucidate its causal a murine model.
Язык: Английский
Процитировано
33
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5862 - 5862
Опубликована: Март 20, 2023
Hematopoietic stem cells (HSCs) support haematopoiesis throughout life and give rise to the whole variety of immune system. Developing in early embryo, passing through precursor stage, maturing into first HSCs, they undergo a fairly large number divisions while maintaining high regenerative potential due repair activity. This is greatly reduced adult HSCs. They go state dormancy anaerobic metabolism maintain their stemness life. However, with age, changes occur pool HSCs that negatively affect effectiveness immunity. Niche aging accumulation mutations age reduces ability self-renew differentiation potential. accompanied by decrease clonal diversity disturbance lymphopoiesis (decrease formation naive T- B-cells) predominance myeloid haematopoiesis. Aging also affects mature cells, regardless HSC, therefore, phagocytic activity intensity oxidative burst decrease, efficiency processing presentation antigens impaired. innate adaptive immunity produce factors form chronic inflammatory background. All these processes have serious negative impact on protective properties system, increasing inflammation, risk developing autoimmune, oncological, cardiovascular diseases age. Understanding mechanisms reducing comparative analysis embryonic features will allow us get closer deciphering programs for development, aging, regeneration rejuvenation
Язык: Английский
Процитировано
27
Circulation, Год журнала: 2024, Номер 149(15)
Опубликована: Март 4, 2024
Nearly 56% of the global population lives in cities, with this number expected to increase 6.6 billion or >70% world's by 2050. Given that cardiometabolic diseases are leading causes morbidity and mortality people living urban areas, transforming cities provisioning systems (or systems) toward health, equity, economic productivity can enable dual attainment climate health goals. Seven provide food, energy, mobility-connectivity, housing, green infrastructure, water management, waste management lie at core human well-being, sustainability. These transcend city boundaries (eg, demand for water, energy is met transboundary supply); thus, entire system a larger construct than local environments. Poorly designed starkly evident worldwide, resulting unprecedented exposures adverse risk factors, including limited physical activity, lack access heart-healthy diets, reduced greenery beneficial social interactions. Transforming health-first approach could be accomplished through integrated spatial planning, along addressing current gaps key systems. Such an will help mitigate undesirable environmental improve cardiovascular metabolic while improving planetary health. The purposes American Heart Association policy statement present conceptual framework, summarize evidence base, outline principles heart-health sustainability outcomes.
Язык: Английский
Процитировано
14
Circulation Research, Год журнала: 2024, Номер 135(9), С. 933 - 950
Опубликована: Сен. 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.
Язык: Английский
Процитировано
10
European Heart Journal, Год журнала: 2025, Номер unknown
Опубликована: Фев. 28, 2025
Graphical AbstractLoss of the Y chromosome (LOY) in blood accelerates progression cardiovascular disease patients with coronary artery (CAD). Weyrich et al. analysed samples from male CAD and found that those >17% LOY white cells had an increased risk mortality fatal myocardial infarction. The authors further observed immune exhibited decreased expression RPS5, serum higher levels contained elevated proinflammatory profibrotic molecules. Additionally, culture supernatant RPS5-knockdown THP-1 was shown to activate human cardiac fibroblasts, inducing their transition a more myofibroblast phenotype.Open new tabDownload slide
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Март 29, 2023
-regulatory elements control gene expression and are dynamic in their structure, reflecting changes to the composition of diverse effector proteins over time
Язык: Английский
Процитировано
20
JACC Basic to Translational Science, Год журнала: 2024, Номер 9(8), С. 956 - 967
Опубликована: Июнь 13, 2024
Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) elusive. The authors performed whole-exome sequencing and deep target among 198 patients with DCM detected germline mutations in cardiomyopathy-related genes somatic CHIP driver genes. Twenty-five were 22 DCM. Ninety-two had pathogenic mutations. Multivariable analysis revealed that was independent risk left ventricular reverse remodeling, irrespective known factors. exacerbated cardiac systolic dysfunction fibrosis a murine model. identification predicts clinical prognosis.
Язык: Английский
Процитировано
7
Current Atherosclerosis Reports, Год журнала: 2023, Номер 25(3), С. 105 - 111
Опубликована: Фев. 18, 2023
Язык: Английский
Процитировано
15