Cardiac Fibrosis: Mechanobiology, Epigenetics, and the Path to Precision Therapy.

IF 3.5 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2026-04-02 eCollection Date: 2026-04-01 DOI:10.1007/s12195-026-00896-z

Mohammad Hamouz, Raneem Y Hammouz, Christine Caruana, Denise Micallef, Andrzej K Bednarek, Philip Dingli

{"title":"Cardiac Fibrosis: Mechanobiology, Epigenetics, and the Path to Precision Therapy.","authors":"Mohammad Hamouz, Raneem Y Hammouz, Christine Caruana, Denise Micallef, Andrzej K Bednarek, Philip Dingli","doi":"10.1007/s12195-026-00896-z","DOIUrl":null,"url":null,"abstract":"Cardiac fibrosis represents a complex pathological process driven by persistent fibroblast activation, dysregulated cardiomyocyte-ECM crosstalk, and maladaptive mechanotransduction, ultimately resulting in myocardial stiffening and progressive heart failure. This review integrates insights from single-cell and spatial transcriptomics, biomechanical studies, and epigenetic profiling to illuminate the cellular heterogeneity and molecular circuits underlying fibrotic remodelling. We highlight emerging therapies including CRISPR-based gene editing, FAP-targeted CAR-T immunotherapy, nanomedicine for selective RNA delivery, and patient-derived cardiac organoids; that collectively position fibrosis as a reversible and actionable target. Finally, we discuss precision medicine strategies leveraging genomics, circulating biomarkers, artificial intelligence, and environmental risk assessment to deliver personalized anti-fibrotic interventions. By uniting mechanobiology, molecular engineering, and clinical innovation, this review charts a translational roadmap toward durable reversal of cardiac fibrosis.Graphical abstract: ","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"19 2","pages":"129-159"},"PeriodicalIF":3.5000,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129132/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and molecular bioengineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s12195-026-00896-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/4/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOPHYSICS","Score":null,"Total":0}

引用次数: 0

Abstract

Cardiac fibrosis represents a complex pathological process driven by persistent fibroblast activation, dysregulated cardiomyocyte-ECM crosstalk, and maladaptive mechanotransduction, ultimately resulting in myocardial stiffening and progressive heart failure. This review integrates insights from single-cell and spatial transcriptomics, biomechanical studies, and epigenetic profiling to illuminate the cellular heterogeneity and molecular circuits underlying fibrotic remodelling. We highlight emerging therapies including CRISPR-based gene editing, FAP-targeted CAR-T immunotherapy, nanomedicine for selective RNA delivery, and patient-derived cardiac organoids; that collectively position fibrosis as a reversible and actionable target. Finally, we discuss precision medicine strategies leveraging genomics, circulating biomarkers, artificial intelligence, and environmental risk assessment to deliver personalized anti-fibrotic interventions. By uniting mechanobiology, molecular engineering, and clinical innovation, this review charts a translational roadmap toward durable reversal of cardiac fibrosis.

Graphical abstract:

查看原文本刊更多论文

心脏纤维化：机械生物学、表观遗传学和精确治疗之路。

心脏纤维化是一个复杂的病理过程，由持续的成纤维细胞激活、失调的心肌细胞- ecm串扰和不适应的机械转导驱动，最终导致心肌硬化和进行性心力衰竭。这篇综述整合了单细胞和空间转录组学、生物力学研究和表观遗传学分析的见解，以阐明纤维化重塑背后的细胞异质性和分子电路。我们重点介绍了新兴疗法，包括基于crispr的基因编辑、fap靶向CAR-T免疫疗法、选择性RNA递送的纳米药物和患者来源的心脏类器官；这些共同将纤维化定位为可逆和可操作的靶标。最后，我们讨论了利用基因组学、循环生物标志物、人工智能和环境风险评估来提供个性化抗纤维化干预的精准医疗策略。通过结合机械生物学、分子工程和临床创新，本综述描绘了心脏纤维化持久逆转的转化路线图。图形化的简介:

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.