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成纤维细胞激活蛋白:将癌症/化疗的认识转向心力衰竭。

Fibroblast activation protein: Pivoting cancer/chemotherapeutic insight towards heart failure.

机构信息

Cell Biology and Anatomy and Cardiovascular Research Center, University of South Carolina School of Medicine and the Columbia VA Health Care System, Columbia, SC, United States.

Yale University Cardiovascular Imaging Center, New Haven CT, United States.

出版信息

Biochem Pharmacol. 2024 Jan;219:115914. doi: 10.1016/j.bcp.2023.115914. Epub 2023 Nov 11.

Abstract

An important mechanism for cancer progression is degradation of the extracellular matrix (ECM) which is accompanied by the emergence and proliferation of an activated fibroblast, termed the cancer associated fibroblast (CAF). More specifically, an enzyme pathway identified to be amplified with local cancer progression and proliferation of the CAF, is fibroblast activation protein (FAP). The development and progression of heart failure (HF) irrespective of the etiology is associated with left ventricular (LV) remodeling and changes in ECM structure and function. As with cancer, HF progression is associated with a change in LV myocardial fibroblast growth and function, and expresses a protein signature not dissimilar to the CAF. The overall goal of this review is to put forward the postulate that scientific discoveries regarding FAP in cancer as well as the development of specific chemotherapeutics could be pivoted to target the emergence of FAP in the activated fibroblast subtype and thus hold translationally relevant diagnostic and therapeutic targets in HF.

摘要

癌症进展的一个重要机制是细胞外基质(ECM)的降解,伴随着激活的成纤维细胞(称为癌相关成纤维细胞,CAF)的出现和增殖。更具体地说,一种被确定与局部癌症进展和 CAF 增殖放大的酶途径是成纤维细胞激活蛋白(FAP)。心力衰竭(HF)的发展和进展与左心室(LV)重构以及 ECM 结构和功能的变化无关。与癌症一样,HF 进展与 LV 心肌成纤维细胞生长和功能的变化有关,并表达与 CAF 相似的蛋白质特征。本综述的总体目标是提出假设,即在癌症中发现 FAP 以及特定化疗药物的发展,可以转向针对激活的成纤维细胞亚型中 FAP 的出现,从而在 HF 中具有具有转化相关性的诊断和治疗靶点。

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