Suppr超能文献

弗里德里希共济失调患者右心室和区域性左心室长轴功能障碍决定因素的差异。

Differences in the determinants of right ventricular and regional left ventricular long-axis dysfunction in Friedreich ataxia.

机构信息

Monash Cardiovascular Research Centre, MonashHeart and Department of Medicine (School of Clinical Sciences at Monash Health), Monash University and Monash Health, Clayton, Victoria, Australia.

Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

出版信息

PLoS One. 2018 Dec 31;13(12):e0209410. doi: 10.1371/journal.pone.0209410. eCollection 2018.

Abstract

BACKGROUND

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which also has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels. We investigated the effects of FRDA on regional long axis function of the left and right ventricles, and also the relationship of long axis systolic (s) and early diastolic (e) peak velocities with GAA repeat number on the shorter (GAA1) and longer FXN alleles (GAA2).

METHODS

The study group of 78 adult subjects (age 32±9 years) with FRDA and normal left ventricular (LV) ejection fraction were compared to 54 healthy control subjects of similar age, sex and body size. Tissue Doppler imaging (TDI) signals were recorded at the mitral annulus for measurement of sand eof the septal, lateral, anterior and inferior walls and at the tricuspid annulus for measurement of right ventricular (RV) sand e.

RESULTS

All the regional LV sand e, and both RV sand RV e, were lower in individuals with FRDA compared to controls (p<0.001 for all). On multivariate analysis, which included LV septal wall thickness (SWT), RV sand RV ewere both inversely correlated with GAA1 (β = -0.32 & -0.33, respectively, p = 0.01), but not with GAA2, whereas anterior and lateral swere both inversely correlated with GAA2 (β = -0.25 and β = -0.28, p = 0.02) but not with GAA1. Increasing SWT was the most consistent LV structural correlate of lower sand e, whereas age was a consistent inverse correlate of ebut not of s`.

CONCLUSION

There are generalized abnormalities of both LV regional and RV long axis function in FRDA, but there are also regional differences in the association of this dysfunction with the smaller and larger GAA repeats in the FXN gene.

摘要

背景

弗里德赖希共济失调(FRDA)是一种常染色体隐性神经退行性疾病,也会对心脏产生影响。在 96%的受影响个体中,FRDA 是由于 FXN 基因内含子 1 中的 GAA 重复扩增的纯合性所致。已经表明 GAA 重复数与 FRDA 中的疾病严重程度有关,这被认为是通过 GAA 重复数与细胞 FXN 水平的反比关系。我们研究了 FRDA 对左、右心室长轴功能的影响,以及长轴收缩期(s)和早期舒张期(e)峰值速度与较短(GAA1)和较长 FXN 等位基因(GAA2)中 GAA 重复数的关系。

方法

本研究组纳入了 78 名 FRDA 成年患者(年龄 32±9 岁),这些患者均具有正常的左心室(LV)射血分数,与 54 名年龄、性别和体型相似的健康对照组进行了比较。应用组织多普勒成像(TDI)技术在二尖瓣环记录 s和 e,测量间隔、侧壁、前壁和下壁的运动,在三尖瓣环记录 s和 e,测量右心室(RV)的运动。

结果

与对照组相比,FRDA 个体的所有 LV 节段 s和 e以及 RV 的 s和 RV e均较低(所有 P<0.001)。多元分析包括 LV 间隔壁厚度(SWT),RV s和 RV e均与 GAA1 呈负相关(β=-0.32 和-0.33,P=0.01),但与 GAA2 无关,而前壁和侧壁 s均与 GAA2 呈负相关(β=-0.25 和-0.28,P=0.02),但与 GAA1 无关。SWT 的增加是 LV 节段 s和 e降低的最一致的结构相关因素,而年龄是 e降低的一致负相关因素,但不是 s`降低的负相关因素。

结论

FRDA 患者存在左心室局部和右心室长轴功能的广泛异常,但这种功能障碍与 FXN 基因中较小和较大 GAA 重复的相关性存在区域性差异。

相似文献

1
Differences in the determinants of right ventricular and regional left ventricular long-axis dysfunction in Friedreich ataxia.
PLoS One. 2018 Dec 31;13(12):e0209410. doi: 10.1371/journal.pone.0209410. eCollection 2018.
2
Early changes in left ventricular long-axis function in Friedreich ataxia: relation with the FXN gene mutation and cardiac structural change.
J Am Soc Echocardiogr. 2011 Jul;24(7):782-9. doi: 10.1016/j.echo.2011.04.004. Epub 2011 May 12.
3
A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia.
J Mol Cell Cardiol. 2011 Nov;51(5):848-54. doi: 10.1016/j.yjmcc.2011.07.001. Epub 2011 Jul 12.
4
Left ventricular structural and functional changes in Friedreich ataxia - Relationship with body size, sex, age and genetic severity.
PLoS One. 2019 Nov 13;14(11):e0225147. doi: 10.1371/journal.pone.0225147. eCollection 2019.
5
Predictors of Left Ventricular Dysfunction in Friedreich's Ataxia in a 16-Year Observational Study.
Am J Cardiovasc Drugs. 2020 Apr;20(2):209-216. doi: 10.1007/s40256-019-00375-z.
6
Insights into the effects of Friedreich ataxia on the left ventricle using T1 mapping and late gadolinium enhancement.
PLoS One. 2024 May 30;19(5):e0303969. doi: 10.1371/journal.pone.0303969. eCollection 2024.
10
A novel GAA-repeat-expansion-based mouse model of Friedreich's ataxia.
Dis Model Mech. 2015 Mar;8(3):225-35. doi: 10.1242/dmm.018952. Epub 2015 Feb 13.

引用本文的文献

1
Insights into the effects of Friedreich ataxia on the left ventricle using T1 mapping and late gadolinium enhancement.
PLoS One. 2024 May 30;19(5):e0303969. doi: 10.1371/journal.pone.0303969. eCollection 2024.
2
Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia.
Hum Gene Ther. 2023 Jul;34(13-14):605-615. doi: 10.1089/hum.2023.020. Epub 2023 Jul 4.
3
Cardiovascular Research in Friedreich Ataxia: Unmet Needs and Opportunities.
JACC Basic Transl Sci. 2022 Jul 13;7(12):1267-1283. doi: 10.1016/j.jacbts.2022.04.005. eCollection 2022 Dec.
4
Myocardial ischaemia reperfusion injury and cardioprotection in the presence of sensory neuropathy: Therapeutic options.
Br J Pharmacol. 2020 Dec;177(23):5336-5356. doi: 10.1111/bph.15021. Epub 2020 Mar 21.
5
Left ventricular structural and functional changes in Friedreich ataxia - Relationship with body size, sex, age and genetic severity.
PLoS One. 2019 Nov 13;14(11):e0225147. doi: 10.1371/journal.pone.0225147. eCollection 2019.
6

本文引用的文献

1
Somatic instability of the expanded GAA repeats in Friedreich's ataxia.
PLoS One. 2017 Dec 19;12(12):e0189990. doi: 10.1371/journal.pone.0189990. eCollection 2017.
3
A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia.
JAMA Neurol. 2015 Nov;72(11):1334-41. doi: 10.1001/jamaneurol.2015.1855.
4
Frataxin levels in peripheral tissue in Friedreich ataxia.
Ann Clin Transl Neurol. 2015 Aug;2(8):831-42. doi: 10.1002/acn3.225. Epub 2015 Jul 1.
7
The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms.
Circulation. 2012 Apr 3;125(13):1626-34. doi: 10.1161/CIRCULATIONAHA.111.059477. Epub 2012 Feb 29.
8
Normal left ventricular ejection fraction and mass but subclinical myocardial dysfunction in patients with Friedreich's ataxia.
Eur Heart J Cardiovasc Imaging. 2012 Apr;13(4):346-52. doi: 10.1093/ejechocard/jer267. Epub 2011 Nov 28.
9
Analysis of echocardiograms in a large heterogeneous cohort of patients with friedreich ataxia.
Am J Cardiol. 2012 Feb 1;109(3):401-5. doi: 10.1016/j.amjcard.2011.09.025. Epub 2011 Nov 10.
10
A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia.
J Mol Cell Cardiol. 2011 Nov;51(5):848-54. doi: 10.1016/j.yjmcc.2011.07.001. Epub 2011 Jul 12.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验