清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Abstract P330: Growth Differentiation Factor 15 Causes Cardiac Cachexia In Heart Failure

GDF15型 心力衰竭 恶病质 医学 内科学 心功能曲线 内分泌学 扩张型心肌病 浪费的 心肌病 心脏纤维化 瘦体质量 生物标志物 心脏病学 癌症 生物 体重 生物化学
作者
Da Young Lee,Zhe Jiao,Andrew Antolic,Daiana Weiss,M. Neale Weitzmann,Michael A. Burke
出处
期刊:Circulation Research [Ovid Technologies (Wolters Kluwer)]
卷期号:129 (Suppl_1) 被引量:1
标识
DOI:10.1161/res.129.suppl_1.p330
摘要

Background: Cachexia is wasting of normal body tissue and occurs in chronic medical diseases. It is a common complication of heart failure (HF) that is associated with very high mortality. Growth differentiation factor 15 (GDF15) regulates food intake and can cause cancer cachexia. GDF15 is a sensitive biomarker in humans, though its biologic function in HF is unknown. This study investigated the role of GDF15 in HF. Methods: We utilized a genetic mouse model of dilated cardiomyopathy (DCM) caused by a mutation in the phospholamban gene (PLN R9C ). PLN R9C mice have dysregulated cardiac calcium handling (a common feature of nearly all forms of HF) and develop progressive DCM that leads to HF and premature death. Q-PCR and ELISA were performed to assess expression, tissue distribution and circulating levels of GDF15 in PLN R9C and age-matched wild type (WT) mice. A double transgenic mouse was created by crossing our DCM model with a constitutive Gdf15 knock-out (KO). Using this novel model, we quantified food intake, and assessed fat and lean tissue mass by tissue weight at necropsy and by dual-energy X-ray absorptiometry (DXA). Cardiac function was assessed using echocardiography, and histochemistry performed to quantify cardiac fibrosis. Survival was assessed by Kaplan-Meier. Results: GDF15 mRNA (43-fold; p<0.01) and protein (54-fold; p<0.01) were increased in LV tissue, and circulating GDF15 was elevated (8.3-fold; p=0.03) in PLN R9C mice. Gdf15 was expressed at low levels and was not increased in other organs in PLN R9C mice. PLN R9C mice developed cachexia (reduced fat and lean mass by tissue weight, reduced fat mass by DXA vs. WT; p<0.01 for all) and consumed less food (p<0.01 vs. WT). Gdf15 KO in PLN R9C preserved fat and lean tissue mass and resulted in higher food intake (p≤0.01 for all). Gdf15 KO had no effect on cardiac structure or function by echocardiography and PLN R9C / Gdf15 KO mice displayed only a small reduction in cardiac fibrosis relative to PLN R9C mice (3%; p<0.01). Despite this, Gdf15 KO prolonged survival in PLN R9C (29±3 vs. 25±3 weeks; p<0.01). Conclusions: GDF15 is a novel cardiac hormone produced in HF that triggers anorexia and cachexia in HF by an extra-cardiac mechanism.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
欣5完成签到 ,获得积分10
44秒前
44秒前
欣6完成签到 ,获得积分10
1分钟前
1分钟前
一颗煤炭完成签到 ,获得积分10
1分钟前
1分钟前
1分钟前
1分钟前
Echan发布了新的文献求助10
1分钟前
1分钟前
成就发夹应助jdj采纳,获得10
1分钟前
紫熊发布了新的文献求助20
2分钟前
2分钟前
able完成签到 ,获得积分10
2分钟前
3分钟前
正直的山雁完成签到,获得积分10
3分钟前
紫熊发布了新的文献求助20
3分钟前
CipherSage应助正直的山雁采纳,获得10
3分钟前
3分钟前
3分钟前
4分钟前
Owen应助正直的山雁采纳,获得10
4分钟前
紫熊发布了新的文献求助20
4分钟前
4分钟前
研友_VZG7GZ应助捋顺爆炸头采纳,获得10
5分钟前
5分钟前
GQ完成签到,获得积分10
6分钟前
6分钟前
科研通AI2S应助科研通管家采纳,获得10
6分钟前
汉堡包应助紫熊采纳,获得10
6分钟前
7分钟前
野椒搞科研完成签到,获得积分10
7分钟前
紫熊完成签到,获得积分10
8分钟前
8分钟前
9分钟前
9分钟前
万能图书馆应助lwenjing采纳,获得10
9分钟前
9分钟前
9分钟前
xin发布了新的文献求助10
10分钟前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Pharmacogenomics: Applications to Patient Care, Third Edition 800
Gerard de Lairesse : an artist between stage and studio 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3081574
求助须知:如何正确求助?哪些是违规求助? 2734437
关于积分的说明 7532784
捐赠科研通 2383903
什么是DOI,文献DOI怎么找? 1264099
科研通“疑难数据库(出版商)”最低求助积分说明 612563
版权声明 597578