Efficacy and safety of optical navigation system versus conventional fluoroscopy in sacral neuromodulation electrode implantation: a prospective randomized controlled trial.

Atherosclerosis is now recognized as a chronic inflammatory disease, a concept with roots extending back to 1858 when Dr. Rudolf Virchow first described inflammatory cell infiltration in the arterial wall. This initial observation was later systematized by Dr. Russell Ross in 1976 through the “response-to-injury” hypothesis, which was subsequently refined in the 1990s to establish the modern “inflammatory hypothesis”. Building upon this foundation, the paradigm was firmly established through accumulating clinical evidence that positioned anti-inflammatory therapy as a new therapeutic avenue. Clinical validation emerged with the CANTOS trial, where canakinumab (150 mg quarterly) targeting IL-1 significantly reduced cardiovascular events independent of lipid-lowering. This breakthrough was followed by evidence confirming colchicine (0.5 mg/day) markedly lowers ischemic cardiovascular risk, leading to its landmark U.S. Food and Drug Administration approval in 2023, while ziltivekimab further demonstrated the promise of IL-6 pathway inhibition. Parallel research identified age-related clonal hematopoiesis of indeterminate potential (CHIP) as a key genetic driver, with mutations (, , , and ) shown to exacerbate atherosclerosis through enhanced pro-inflammatory responses, , , . This cardiovascular risk is quantitatively governed by the hematopoietic stem cell proliferation rate in a unidirectional relationship. The expansion of the mutant hematopoietic clone is unaffected by subclinical atherosclerosis. More recently, dietary studies revealed that an alternating high-fat diet (HFD) exacerbates plaques IL-1-dependent neutrophilia and neutrophil extracellular traps (NETs), while an early intermittent high-cholesterol diet exacerbates atherosclerosis by altering the quantity and phenotype of artery-resident macrophages and disrupting key pathways such as actin filament organization. Another recent line of evidence demonstrates that cyclic long-chain ceramides exacerbate atherosclerosis by binding to G protein-coupled receptors (GPCRs), activating the G signaling pathway and NLRP3 inflammasome, and promoting IL-1 release (). Timeline of key milestones in inflammation and atherosclerosis research (1858–2025). Abbreviations: AIM2, absent in melanoma 2; CHIP, age-related clonal hematopoiesis of indeterminate potential; Dmnt3a, DNA methyltransferase 3 alpha; FDA, Food and Drug Administration; Gq, Gq protein; GPCRs, G protein-coupled receptors; IL-1, interleukin-1; IL-6, interleukin-6; JAK2, Janus kinase 2; LDL, low-density lipoprotein; MACE, major adverse cardiovascular events; MI, myocardial infarction; NETosis, neutrophil extracellular trap formation; NLRP3, NOD-like receptor thermal protein domain associated protein 3; Tet2, tet methylcytosine dioxygenase 2. Atherosclerosis initiates with the accumulation of lipids in the vessel wall, where retained lipoproteins such as LDL become modified ( oxidation and glycation, etc.) and trigger the release of chemokines from endothelial cells and vascular smooth muscle cells (VSMCs). This promotes the recruitment of monocytes and neutrophils. Monocytes differentiate into macrophages that engulf lipids to form foam cells. Intracellular cholesterol crystals or oxidized LDL can activate the NLRP3 inflammasome, amplifying pro-inflammatory signaling. NETs further enhance monocyte recruitment, macrophage activation, and VSMC injury. Sustained inflammation drives plaque progression. VSMCs migrate into the intima and produce matrix to form a stabilizing fibrous cap. However, under lipid and inflammatory stimulation, VSMCs undergo phenotypic switching, reducing matrix synthesis and increasing inflammation, which thins the fibrous cap. Concurrently, foam cells, VSMCs, and other cells undergo apoptosis, necroptosis, and other types of cell death due to lipid toxicity and inflammatory damage, forming a lipid-rich necrotic core that exacerbates local inflammation ().