Hospital of the University of Pennsylvania Philadelphia PA USA.
University of Pennsylvania Perelman School of Medicine Philadelphia PA USA.
J Am Heart Assoc. 2024 Sep 3;13(17):e033675. doi: 10.1161/JAHA.123.033675. Epub 2024 Aug 29.
The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach.
We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or HF hospital admission. We also assessed the relationship of each SASP factor to 4746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Two SASP factors were identified. Both factors were associated with older age, lower estimated glomerular filtration rate, and more advanced New York Heart Association class, among other clinical variables. Both SASP factors exhibited a significant positive association with the risk of death independent of the Meta-Analysis of Global-Group in Chronic HF score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The 2 identified SASP factors were associated with 1201 and 1554 proteins, respectively, belonging to various pathways including the coagulation system, complement system, acute phase response signaling, and retinoid X receptor-related pathways that regulate cell metabolism.
Increased SASP components are independently associated with adverse outcomes in HF. Biologic pathways associated with SASP are predominantly related to coagulation, inflammation, and cell metabolism.
细胞衰老在人类心力衰竭（HF）中的作用仍不清楚。衰老相关分泌表型（SASP）由衰老细胞释放的蛋白质组成。我们使用血浆蛋白质组学方法评估了 SASP 与人类 HF 的预后意义和生物学途径。
我们使用 SOMAScan V4 测定法在 2248 名 PHFS（宾夕法尼亚 HF 研究）参与者中测量了 25 种已知的 SASP 蛋白。我们提取这些蛋白质中的共同方差以生成 SASP 因子得分，并评估这些 SASP 因子得分与（1）全因死亡和（2）死亡或 HF 住院的复合终点之间的关系。我们还评估了每个 SASP 因子与其他 4746 种蛋白质之间的关系，同时进行了多变量校正，随后进行了途径分析。确定了两个 SASP 因子。这两个因子都与年龄较大、估计肾小球滤过率较低以及纽约心脏协会（NYHA）分级较高有关，此外还与其他临床变量有关。在不考虑慢性 HF 全球组荟萃分析评分和 NT-proBNP（N 末端 pro-B 型利钠肽）水平的情况下，两个 SASP 因子均与死亡风险呈显著正相关。这两个 SASP 因子分别与 1201 种和 1554 种蛋白质相关，这些蛋白质分别属于各种途径，包括凝血系统、补体系统、急性期反应信号和调节细胞代谢的视黄醇 X 受体相关途径。
SASP 成分的增加与 HF 的不良预后独立相关。与 SASP 相关的生物学途径主要与凝血、炎症和细胞代谢有关。
