Vol. 3 No. 2 (2026): April - June
73-84
2026-06-29
Open Access

The PRMT–ADMA–DDAH Axis in Cardiovascular Disease: Linking Protein Arginine Methylation to Endothelial Dysfunction and Vascular Remodeling.

Munisakhon Makhkamova
Nargiza Nurillaeva
https://doi.org/10.70626/cardiouz-2026-3-00090

Received: 2026-02-28

Published: 2026-06-29

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Abstract

Endothelial dysfunction is a central pathophysiological process underlying the initiation and progression of cardiovascular disease and is characterized by impaired nitric oxide (NO) bioavailability, increased oxidative stress, inflammation, vasoconstriction, and prothrombotic vascular signaling. Among the endogenous regulators of the NO pathway, asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has emerged as an important molecular link between metabolic stress and vascular dysfunction. However, circulating ADMA represents only one component of a broader regulatory network involving protein arginine methyltransferases (PRMTs), dimethylarginine dimethylaminohydrolases (DDAHs), and alternative methylarginine-metabolizing pathways. This review examines the molecular architecture of the PRMT–ADMA–DDAH–eNOS/NO axis and its contribution to atherosclerosis, coronary artery disease, hypertension, heart failure, cardiometabolic disorders, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease. Finally, we discuss the therapeutic potential and limitations of targeting PRMT activity, ADMA metabolism, DDAH1, AGXT2, and NO bioavailability. Understanding this regulatory network may provide a mechanistic framework for identifying endothelial phenotypes of residual cardiovascular risk and developing more individualized strategies for cardiovascular prevention and treatment.

Keywords

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About the Authors

Munisakhon Makhkamova
md_munisakhon@mail.ru
Tashkent Medical Academy
https://orcid.org/0000-0002-2658-6148 (unauthenticated)
Nargiza Nurillaeva
nargizanur@yandex.ru
Tashkent State Medical University

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How to Cite

The PRMT–ADMA–DDAH Axis in Cardiovascular Disease: Linking Protein Arginine Methylation to Endothelial Dysfunction and Vascular Remodeling. (M. Makhkamova & N. Nurillaeva, Trans.). (2026). CARDIOLOGY OF UZBEKISTAN, 3(2), 73-84. https://doi.org/10.70626/cardiouz-2026-3-00090
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