Phosphoproteomics in Vascular Biology and Disease: Illuminating Signaling in the Vessel

Phosphoregulatory events underlie vascular responses to environmental and pathological stimuli, regulate hemostasis and thrombosis, and drive vascular remodeling in health and disease. Consequently, defining phosphorylation-dependent signaling networks in vascular physiology and pathology has enabled biomarker discovery and informed therapeutic interventions. Advances in mass spectrometry-based phosphoproteomics have enabled accurate and high-resolution mapping of dynamic phosphorylation events at the systems level, providing comprehensive mechanistic insights into vascular signaling and pathology. In this review, we contextualize phosphorylation in the vascular niche and summarize the current state of phosphoproteomics in vascular research, highlighting experimental design considerations, technological advances, quantification strategies, and data analysis approaches to uncover biological insights from large-scale phosphoproteomic data sets. Finally, we discuss recent discoveries in vascular signaling and disease, along with current challenges and emerging directions for applying phosphoproteomics to critical questions in vascular biology.