Tahir Usman A, Kolm Paul, Kwong Raymond Y, Desai Milind Y, Dolman Sarahfaye F, Deng Shuliang, Appelbaum Evan, Desvigne-Nickens Patrice, DiMarco John P, Tiwari Gaurav, Friedrich Matthias G, Zelaya-Portillo Julissa H, Jerosch-Herold Michael, Kim Dong-Yun, Maron Martin S, Piechnik Stefan K, Schulz-Menger Jeanette, Watkins Hugh, Weintraub William S, Neubauer Stefan, Kramer Christopher M, Jarolim Petr, Gerszten Robert E, Ho Carolyn Y
Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (U.A.T., S.D., E.A., G.T., R.E.G.).
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (P.K., S.K.P., H.W., S.N.).
Circ Heart Fail. 2024 Dec;17(12):e011707. doi: 10.1161/CIRCHEARTFAILURE.124.011707. Epub 2024 Nov 5.
Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition that can lead to atrial fibrillation, heart failure, and sudden cardiac death in many individuals but mild clinical impact in others. The mechanisms underlying this phenotypic heterogeneity are not well defined. The aim of this study was to use plasma proteomic profiling to help illuminate biomarkers that reflect or inform the heterogeneity observed in HCM.
The Olink antibody-based proteomic platform was used to measure plasma proteins in patients with genotype positive (sarcomeric) HCM participating in the HCM Registry. We assessed associations between plasma protein levels with clinical features, cardiac magnetic resonance imaging metrics, and the development of atrial fibrillation.
We measured 275 proteins in 701 patients with sarcomeric HCM. There were associations between late gadolinium enhancement with proteins reflecting neurohormonal activation (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and ACE2 [angiotensin-converting enzyme 2]). Metrics of left ventricular remodeling had novel associations with proteins involved in vascular development and homeostasis (vascular endothelial growth factor-D and TM [thrombomodulin]). Assessing clinical features, the European Society of Cardiology sudden cardiac death risk score was inversely associated with SCF (stem cell factor). Incident atrial fibrillation was associated with mediators of inflammation and fibrosis (MMP2 [matrix metalloproteinase 2] and SPON1 [spondin 1]).
Proteomic profiling of sarcomeric HCM identified biomarkers associated with adverse imaging and clinical phenotypes. These circulating proteins are part of both established pathways, including neurohormonal activation and fibrosis, and less familiar pathways, including endothelial function and inflammatory proteins less well characterized in HCM. These findings highlight the value of plasma profiling to identify biomarkers of risk and to gain further insights into the pathophysiology of HCM.
肥厚型心肌病（HCM）是一种异质性疾病，可导致许多患者发生心房颤动、心力衰竭和心源性猝死，但对其他一些患者的临床影响较轻。这种表型异质性的潜在机制尚不清楚。本研究的目的是利用血浆蛋白质组学分析来帮助阐明反映或提示HCM中观察到的异质性的生物标志物。
采用基于Olink抗体的蛋白质组学平台，对参与HCM注册研究的基因型阳性（肌节性）HCM患者的血浆蛋白进行检测。我们评估了血浆蛋白水平与临床特征、心脏磁共振成像指标以及心房颤动发生之间的关联。
我们对701例肌节性HCM患者的275种蛋白质进行了检测。钆延迟强化与反映神经激素激活的蛋白质（N末端B型利钠肽原[NT-proBNP]和血管紧张素转换酶2[ACE2]）之间存在关联。左心室重构指标与参与血管发育和稳态的蛋白质（血管内皮生长因子-D和血栓调节蛋白[TM]）有新的关联。在评估临床特征时，欧洲心脏病学会心源性猝死风险评分与干细胞因子（SCF）呈负相关。新发心房颤动与炎症和纤维化介质（基质金属蛋白酶2[MMP2]和脊髓灰质炎病毒1[SPON1]）有关。
肌节性HCM的蛋白质组学分析确定了与不良影像学和临床表型相关的生物标志物。这些循环蛋白是既定通路（包括神经激素激活和纤维化）以及较少为人所知的通路（包括内皮功能和在HCM中特征不太明确的炎症蛋白）的一部分。这些发现凸显了血浆分析在识别风险生物标志物以及深入了解HCM病理生理学方面的价值。
