Proteomic architecture of frailty across the spectrum of cardiovascular disease.
Proteomic architecture of frailty across the spectrum of cardiovascular disease.
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作者：
虽然脆弱是人口老龄化的一个突出的危险因素，但脆弱的潜在生物学尚未得到完整的描述。在这项研究中，我们对809名接受经导管主动脉瓣植入术的严重主动脉瓣狭窄患者进行了前瞻性发现队列研究，整合了979种循环蛋白，涉及广泛的生理机能和12项脆弱性指标。我们的目的是在一个高度易感人群中描述脆弱的蛋白质组学结构，并研究其与临床结果和全系统表型的关系，以定义潜在的新的、临床相关的脆弱生物学。蛋白质组学特征（特别是身体功能）与AS干预后的结果相关，指明了先天免疫、细胞生长/衰老、纤维化/代谢的途径，以及一系列在人类衰老中未被广泛描述的蛋白质。在已发表的队列中，“脆弱蛋白质组”显示出不同年龄（20-100岁，年龄只能解释一小部分方差）的异质性轨迹，并且在两个广泛的验证队列（N > 35,000）中与心脏和非心脏表型和结果相关，时间约为20 - 30年。这些发现表明，在与年龄相关的发病率和虚弱中，精确的多器官健康状况生物标志物的重要性。我们的研究包括观察性队列研究，以确定循环，脆弱的蛋白质组学标记，并检查“脆弱蛋白质组”与多病症和长期结局的关系。
While frailty is a prominent risk factor in an aging population, the underlying biology of frailty is incompletely described. Here, we integrate 979 circulating proteins across a wide range of physiologies with 12 measures of frailty in a prospective discovery cohort of 809 individuals with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation. Our aim was to characterize the proteomic architecture of frailty in a highly susceptible population and study its relation to clinical outcome and systems‐wide phenotypes to define potential novel, clinically relevant frailty biology. Proteomic signatures (specifically of physical function) were related to post‐intervention outcome in AS, specifying pathways of innate immunity, cell growth/senescence, fibrosis/metabolism, and a host of proteins not widely described in human aging. In published cohorts, the “frailty proteome” displayed heterogeneous trajectories across age (20–100 years, age only explaining a small fraction of variance) and were associated with cardiac and non‐cardiac phenotypes and outcomes across two broad validation cohorts (N > 35,000) over ≈2–3 decades. These findings suggest the importance of precision biomarkers of underlying multi‐organ health status in age‐related morbidity and frailty. Our study involved observational cohort studies to identify circulating, proteomic markers of frailty and examine the relation of the “frailty proteome” with multimorbidity and long‐term outcomes.
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DOI：
10.1161/circimaging.110.958884
发表时间：
2010-09
期刊：
Circulation. Cardiovascular imaging
影响因子：
--
作者：
Fox CS;Massaro JM;Schlett CL;Lehman SJ;Meigs JB;O'Donnell CJ;Hoffmann U;Murabito JM
通讯作者：
Murabito JM
DOI：
10.1016/j.bbrc.2009.03.014
发表时间：
2009-05-01
影响因子：
3.1
作者：
Carlsson, Lena M. S.;Jacobson, Peter;Walley, Andrew;Froguel, Philippe;Sjostrom, Lars;Svensson, Per-Arne;Sjoholm, Kajsa
通讯作者：
Sjoholm, Kajsa
影响因子：
5.5
作者：
Alonso-Martin S;Rochat A;Mademtzoglou D;Morais J;de Reyniès A;Auradé F;Chang TH;Zammit PS;Relaix F
通讯作者：
Relaix F
影响因子：
4.6
作者：
Nunoue T;Yamaguchi S;Teshigawara S;Katayama A;Nakatsuka A;Eguchi J;Niki T;Wada J
通讯作者：
Wada J
DOI：
10.1046/j.1532-5415.2003.51465.x
发表时间：
2003-10-01
影响因子：
6.3
作者：
Borson, S;Scanlan, JM;Ganguli, M
通讯作者：
Ganguli, M