Authors
Durlav Chowdhury, Saptarshi Mukherjee, Priyanka Dubey, Sarvesh K Paliwal, Devi Prasad Pandey, Surendra H Bodakhe
Published in
Journal of receptor and signal transduction research. Pages 1-10. Oct 15, 2026. Epub Oct 15, 2026.
Abstract
Atherosclerosis is primarily induced by endothelial dysfunction, a pivotal initial occurrence that transforms the arterial wall from a dormant barrier to a pro-inflammatory, pro-thrombotic condition. G protein-coupled receptors (GPCRs) serve as essential sensors governing homeostasis, rendering them crucial therapeutic targets. Nonetheless, conventional unbiased GPCR medications sometimes provoke dose-limiting systemic adverse effects due to pleiotropic transducer engagement and widespread on-target activity across non-vascular tissue beds. Biased GPCR signaling constitutes a revolutionary pharmaceutical paradigm that addresses these constraints. By employing strategically chosen ligands or allosteric modulators that stabilize certain receptor conformations, one can selectively activate vasoprotective, barrier-enhancing pathways while dissociating harmful inflammatory responses. This paper examines the mechanisms of functional selectivity among main endothelium GPCR families, including angiotensin II, sphingosine-1-phosphate, atypical chemokine, and β-adrenergic receptors. Additionally, we highlight the potential of high-resolution structural biology, single-cell transcriptomics, spatial omics, and dynamic bioengineered models as emerging translational instruments to guide future drug discovery. Engineering endothelium-targeted biased therapies is a precise, pathway-specific approach to halt plaque progression, stabilize susceptible lesions, and transform the future of precision cardiovascular care.
PMID:
42878053
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.
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