fig2
Figure 2. Integrated mechanisms of panvascular aging. Multiple interdependent processes - including NO decline, glycocalyx thinning, shear stress vulnerability, chronic inflammation, oxidative stress, VSMCs dysfunction, senescence, ECM remodeling, epigenetic reprogramming, and brain-vascular axis disruption - converge to accelerate systemic vascular deterioration and organ injury. Therapeutic strategies targeting BH4/NO signaling, AMPK activation, glycocalyx restoration, mechanotransduction reprogramming, anti-inflammatory interventions, mitochondrial protection, senotherapies, ECM modulation, and epigenetic/microRNA pathways hold promise for mitigating panvascular aging. The figure was created with https://app.biorender.com/citation/68c8320f7eaabe5720f1b2d6. ECs: Endothelial cells; VSMCs: vascular smooth muscle cells; NO: nitric oxide; AMPK: adenosine monophosphate-activated protein kinase; ECM: extracellular matrix; ROS: reactive oxygen species; eNOS: endothelial NO synthase; GCH1: guanosine triphosphate cyclohydrolase 1; BBB: blood-brain barrier; SASP: senescence-associated secretory phenotype; MMPs: matrix metalloproteinases; AGEs: advanced glycation end-products; TIMPs: tissue inhibitor of metalloproteinases; YAP: yes-associated protein; TAZ: transcriptional coactivator with PDZ-binding motif; NMN: nicotinamide mononucleotide; NR: nicotinamide riboside; KLF4/2: Krüppel-like factor4/2; CHIP: clonal hematopoiesis of indeterminate potential; LoDoCo2: Low-dose colchicine 2; COLCOT: colchicine cardiovascular outcomes trial; IL-1β: interleukin-1 beta; CANTOS: canakinumab anti-inflammatory thrombosis outcomes study; EPC: endothelial progenitor cell; HS: heparan sulfate; JAK: Janus kinase; cGAS-STING: cyclic GMP-AMP synthase-stimulator of interferon genes; PECAM1: platelet and endothelial cell adhesion molecule 1; VEGFR2: vascular endothelial growth factor receptor 2; TRP channels: transient receptor potential channels; RUNX2: RUNX family transcription factor 2; HuR: human antigen R; YTHDF2: YTH N6-methyladenosine RNA binding protein F2.
