Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.
Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.
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DOI：
10.1161/jaha.122.029980
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发表时间：
2023-11-07
影响因子：
5.4
通讯作者：
Nayor, Matthew
中科院分区：
文献类型：
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作者：
Shah, Ravi V.;Hwang, Shih-Jen;Murthy, Venkatesh L.;Zhao, Shilin;Tanriverdi, Kahraman;Gajjar, Priya;Duarte, Kevin;Schoenike, Mark;Farrell, Robyn;Brooks, Liana C.;Gopal, Deepa M.;Ho, Jennifer E.;Girerd, Nicholas;Vasan, Ramachandran S.;Levy, Daniel;Freedman, Jane E.;Lewis, Gregory D.;Nayor, Matthew
虽然运动障碍是射血分数保留型心力衰竭 (HFpEF) 的症状和诊断的核心，但之前对 HFpEF 生物标志物的研究主要集中在静息表型。我们将精确的运动表型与心血管蛋白质组学相结合，以确定 HFpEF 运动反应的蛋白质特征和新的潜在治疗靶点。我们通过心肺运动测试和侵入性监测分析了 151 名个体（N=103 HFpEF，48 名对照；62±11 岁；56% 女性）的 277 种蛋白质 (Olink)。使用根据年龄/性别调整的岭回归，我们定义了 HFpEF 涉及的 5 个生理变量的蛋白质组学特征：峰值摄氧量、峰值心输出量、肺毛细血管楔压/心输出量斜率、峰值肺血管阻力和峰值外周 O2 提取。每种运动表型的多蛋白特征捕获了各自运动表型中很大一部分的差异。询问每个特征中特定蛋白质的重要性（脊系数大小），突出显示与 HFpEF 病理生理学相关的假定蛋白质（例如炎症、促纤维化蛋白质），以及与不同生理学相关的新蛋白质（例如涉及多器官 [肾脏、肝脏、肌肉、脂肪] 健康的蛋白质）与 O2 提取受损有关。在一个单独的样本中（N = 522，261 次 HF 事件），峰值摄氧量和肺毛细血管楔压/心输出量斜率的蛋白质组特征与 HFpEF 事件相关（优势比分别为 0.67 [95% CI，0.50–0.90] 和 1.43 [95% CI，1.11–1.85]），并调整临床因素和 B 型 利尿钠肽。心血管蛋白质组与 HFpEF 的精确运动表型相关，这表明了新的机制目标和风险分层的潜在方法，以在发病机制早期预防 HFpEF。
While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets. We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O2 extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins), and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O2 extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50–0.90] and 1.43 [95% CI, 1.11–1.85], respectively) with adjustment for clinical factors and B‐type natriuretic peptides. The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis.
影响因子：
4.7
作者：
Paul P;Picard C;Lyonnet L;Resseguier N;Hubert L;Arnaud L;Di Cristofaro J;Laine M;Paganelli F;Dignat-George F;Frère C;Sabatier F;Guieu R;Bonello L
通讯作者：
Bonello L
影响因子：
4.6
作者：
Liu SQ;Troy JB;Luan CH;Guillory RJ
通讯作者：
Guillory RJ