Molecular Regulation and Mechanisms of Nitric Oxide in Endothelial Cells and Beyond

Dear Colleagues,

Nitric oxide (NO) is a ubiquitous and vital signaling molecule that integrates function across organ systems. Its synthesis by nitric oxide synthase (NOS) isoforms—endothelial (eNOS), neuronal (nNOS), and inducible (iNOS)—initiates diverse and cell-specific signaling cascades. While the endothelium remains a paradigm for understanding NO's role in vascular homeostasis, a comprehensive view of NO biology requires exploration of its distinct and synergistic actions in the entire cellular ecosystem.

This Special Issue aims to provide a deep mechanistic insight into the molecular regulation of NO production and its downstream effects both within endothelial cells and in other critical cell types. We seek to highlight how cell-specific contexts—from the enzymes expressed to the unique interactomes and redox environments—shape the functional outcome of NO signaling in health and disease.

We welcome the submission of original research, reviews, and perspectives that explore the molecular world of NO. We encourage submissions that focus on the following:

• Cell-Specific NOS Regulation and Signaling:
  
  • Endothelial Cells: Novel mechanisms in eNOS coupling/uncoupling, post-translational control, calcium signaling, and receptor-mediated activation.
  • Beyond Endothelium: Regulation of nNOS in neurons and skeletal muscle; molecular control of iNOS expression and degradation in immune cells; and atypical NO production in non-canonical cells.
• Organ-Specific NO Mechanisms: Comparative studies of NO signaling in the vasculature, nervous system, heart, kidney, liver, immune system, and reproductive organs.
• Cross-Talk and Systemic Communication: Research on how NO derived from one cell type (e.g., endothelial NO) influences the function of another (e.g., neurons, cardiomyocytes, platelets, or immune cells), and vice versa.
• Novel Downstream Effectors: Discovery of unique protein targets for S-nitrosylation, nitration, or guanylyl cyclase activation in specific cellular environments.
• Therapeutic Targeting: Cell-specific strategies to modulate NO bioavailability or signaling pathways for treating cardiovascular, neurodegenerative, inflammatory, and metabolic diseases.

By integrating research on endothelial cells with investigations into other cell types, this issue will foster a holistic, modern understanding of NO's multifaceted roles. We aim to illuminate the intricate molecular dialogue orchestrated by NO across the cellular landscape, paving the way for precise therapeutic interventions.

Prof. Dr. Roberto Berra-Romani
Prof. Dr. Francesco Moccia
Guest Editors

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