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

Deciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges DOI Open Access
Suzanne M. Watt, Maria G. Roubelakis

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

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