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肥胖与意义未明的克隆性造血:心血管疾病和恶性肿瘤中的同盟因素

Obesity and Clonal Hematopoiesis of Indeterminate Potential: Allies in Cardiovascular Diseases and Malignancies.

作者信息

Komic Luka, Kumric Marko, Urlic Hrvoje, Rizikalo Azer, Grahovac Marko, Kelam Jelena, Tomicic Marion, Rusic Doris, Ticinovic Kurir Tina, Bozic Josko

机构信息

Department of Family Medicine, Split-Dalmatia County Health Center, 21000 Split, Croatia.

Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia.

出版信息

Life (Basel). 2023 Jun 10;13(6):1365. doi: 10.3390/life13061365.

DOI:10.3390/life13061365
PMID:37374147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10304718/
Abstract

The clonal hematopoiesis of indeterminate potential (CHIP) is a term used to describe individuals who have detectable somatic mutations in genes commonly found in individuals with hematologic cancers but without any apparent evidence of such conditions. The mortality rate in individuals with CHIP is remarkably higher than the influence ascribed to hematologic malignancies, and it is plausible that cardiovascular diseases (CVD) could elucidate the apparent disparity. Studies have shown that the most frequently altered genes in CHIP are associated with the increased incidence of CVDs, type 2 diabetes mellitus (T2DM) and myeloid malignancies, as well as obesity. Additionally, multiple research studies have confirmed that obesity is also independently associated with these conditions, particularly the development and progression of atherosclerotic CVD. Considering the shared pathogenetic mechanisms of obesity and CHIP, our objective in this review was to investigate both preclinical and clinical evidence regarding the correlation between obesity and CHIP and the resulting implications of this interaction on the pathophysiology of CVDs and malignancies. The pro-inflammatory condition induced by obesity and CHIP enhances the probability of developing both diseases and increases the likelihood of developing CVDs, T2DM and malignancies, suggesting that a dangerous vicious loop may exist. However, it is vital to conduct additional research that will suggest targeted treatment options for obese individuals with CHIP in order to reduce harmful effects connected to these conditions.

摘要

不确定潜能的克隆性造血(CHIP)是一个术语,用于描述那些在血液系统癌症患者中常见基因里有可检测到的体细胞突变,但没有任何此类疾病明显证据的个体。CHIP个体的死亡率显著高于归因于血液系统恶性肿瘤的影响,心血管疾病(CVD)可能解释这种明显差异这一点是合理的。研究表明,CHIP中最常发生改变的基因与CVD、2型糖尿病(T2DM)、髓系恶性肿瘤以及肥胖症的发病率增加有关。此外,多项研究证实,肥胖也与这些疾病独立相关,尤其是动脉粥样硬化性CVD的发生和发展。考虑到肥胖和CHIP共同的发病机制,我们在这篇综述中的目标是研究关于肥胖与CHIP之间相关性的临床前和临床证据,以及这种相互作用对CVD和恶性肿瘤病理生理学的影响。肥胖和CHIP诱导的促炎状态增加了患这两种疾病的可能性,并增加了患CVD、T2DM和恶性肿瘤的可能性,这表明可能存在一个危险的恶性循环。然而,开展更多研究以提出针对患有CHIP的肥胖个体的靶向治疗方案,从而减少与这些疾病相关的有害影响至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/077f/10304718/87ca96f7ede2/life-13-01365-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/077f/10304718/2c9d87a13f7a/life-13-01365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/077f/10304718/87ca96f7ede2/life-13-01365-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/077f/10304718/2c9d87a13f7a/life-13-01365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/077f/10304718/87ca96f7ede2/life-13-01365-g002.jpg

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Diabetes Care. 2023 Nov 1;46(11):1978-1985. doi: 10.2337/dc23-0805.
2
Obesity and Cardiovascular Risk: Systematic Intervention Is the Key for Prevention.肥胖与心血管风险:系统干预是预防的关键。
Healthcare (Basel). 2023 Mar 21;11(6):902. doi: 10.3390/healthcare11060902.
3
Role of ASXL1 in hematopoiesis and myeloid diseases.ASXL1 在造血和髓系疾病中的作用。
Exp Hematol. 2022 Nov;115:14-19. doi: 10.1016/j.exphem.2022.09.003. Epub 2022 Sep 30.
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Obesity: a perfect storm for carcinogenesis.肥胖:致癌作用的完美风暴。
Cancer Metastasis Rev. 2022 Sep;41(3):491-515. doi: 10.1007/s10555-022-10046-2. Epub 2022 Aug 30.
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Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation.肥胖与心血管疾病:机制洞察与管理策略。世界心脏联盟和世界肥胖联盟联合立场文件。
Eur J Prev Cardiol. 2022 Dec 7;29(17):2218-2237. doi: 10.1093/eurjpc/zwac187.
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Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk.体细胞突变和克隆性造血作为与年龄相关的心血管风险的驱动因素。
Curr Cardiol Rep. 2022 Aug;24(8):1049-1058. doi: 10.1007/s11886-022-01724-2. Epub 2022 Jun 3.
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Elife. 2022 May 30;11:e72359. doi: 10.7554/eLife.72359.
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