Angiotensin II-Induced Cardiac Fibrosis: Genomic and Molecular Drivers, Emerging Biomarkers and Therapeutic Perspectives
- 1Unidad de Investigación Epidemiológica en Endocrinología y Nutrición, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
- 2Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 03100, Mexico
Abstract
Chronically elevated angiotensin II (Ang II) drives adverse cardiac remodelling, converting a reparative response into progressive interstitial and perivascular fibrosis that stiffens the ventricle and precedes overt heart failure. Acting through the angiotensin II type 1 receptor, Ang II generates reactive oxygen species, recruits and polarises immune cells and activates resident fibroblasts, converging on transforming growth factor-β (TGF-β)-dependent and mechanotransductive programmes that drive myofibroblast differentiation and excessive extracellular matrix (ECM) deposition. The magnitude of this response varies between patients: germline variation in renin–angiotensin–aldosterone system (RAAS) genes, loci for heart failure and imaging-defined fibrosis, epigenomic reprogramming of the fibroblast, non-coding RNA networks and metabolic rewiring of collagen-producing cells all modulate the transition from compensated hypertrophy to fibrotic failure. This review integrates these genomic, epigenomic, transcriptomic and metabolomic layers with the signalling architecture of Ang II-induced fibrosis, and reviews the circulating biomarkers—collagen turnover peptides, matricellular and immune mediators, non-coding RNAs and cell-free DNA methylation signatures—that could detect fibrotic activity before remodelling becomes irreversible. We then consider why fibrosis regression under RAAS blockade appears heterogeneous, which emerging targets are mechanistically credible, and how genotype–biomarker–imaging phenotyping could enrich antifibrotic trials. Priorities for ancestrally diverse cohorts and standardised biomarker methodology are identified.
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BibTeX
@article{martinezrodriguez2026angiotensin,
title = {{Angiotensin II-Induced Cardiac Fibrosis: Genomic and Molecular Drivers, Emerging Biomarkers and Therapeutic Perspectives}},
author = {Nancy Lucero Martínez-Rodríguez and Javier Alonzo Campos-González and César López-Camarillo and Oscar Medina-Contreras},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219944},
url = {https://www.mdpi.com/1422-0067/27/21/9944},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Angiotensin II-Induced Cardiac Fibrosis: Genomic and Molecular Drivers, Emerging Biomarkers and Therapeutic Perspectives
AU - Nancy Lucero Martínez-Rodríguez
AU - Javier Alonzo Campos-González
AU - César López-Camarillo
AU - Oscar Medina-Contreras
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219944
UR - https://www.mdpi.com/1422-0067/27/21/9944
AB - Chronically elevated angiotensin II (Ang II) drives adverse cardiac remodelling, converting a reparative response into progressive interstitial and perivascular fibrosis that stiffens the ventricle and precedes overt heart failure. Acting through the angiotensin II type 1 receptor, Ang II generates reactive oxygen species, recruits and polarises immune cells and activates resident fibroblasts, converging on transforming growth factor-β (TGF-β)-dependent and mechanotransductive programmes that drive myofibroblast differentiation and excessive extracellular matrix (ECM) deposition. The magnitude of this response varies between patients: germline variation in renin–angiotensin–aldosterone system (RAAS) genes, loci for heart failure and imaging-defined fibrosis, epigenomic reprogramming of the fibroblast, non-coding RNA networks and metabolic rewiring of collagen-producing cells all modulate the transition from compensated hypertrophy to fibrotic failure. This review integrates these genomic, epigenomic, transcriptomic and metabolomic layers with the signalling architecture of Ang II-induced fibrosis, and reviews the circulating biomarkers—collagen turnover peptides, matricellular and immune mediators, non-coding RNAs and cell-free DNA methylation signatures—that could detect fibrotic activity before remodelling becomes irreversible. We then consider why fibrosis regression under RAAS blockade appears heterogeneous, which emerging targets are mechanistically credible, and how genotype–biomarker–imaging phenotyping could enrich antifibrotic trials. Priorities for ancestrally diverse cohorts and standardised biomarker methodology are identified.
SN - 1422-0067
ER -