{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:27:51Z","timestamp":1791408471869,"version":"4.3.3"},"reference-count":100,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU NextGenerationEU through the Recovery and Resilience Plan for Slovakia","award":["09I03-03-V05-00008"],"award-info":[{"award-number":["09I03-03-V05-00008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Atherosclerosis is a chronic, progressive disease of the arterial wall and the principal pathological substrate underlying most cardiovascular diseases, including ischemic heart disease, stroke, and peripheral arterial disease. Despite advances in prevention, imaging, and therapy, atherosclerosis remains the leading cause of cardiovascular morbidity and mortality worldwide. From a pathological perspective, the disease represents a dynamic and heterogeneous process characterized by endothelial dysfunction, lipid retention and modification, chronic inflammation, immune activation, smooth muscle cell phenotypic modulation, extracellular matrix remodeling, and thrombogenic surface alterations. This review provides a comprehensive overview of atherosclerosis from a pathologist\u2019s perspective, integrating classical morphological concepts with contemporary insights into immunopathology, plaque classification, and mechanisms of plaque instability. We summarize the structure and function of the arterial wall, the stepwise pathogenesis of lesion initiation and progression, and the histopathological classification systems established by the American Heart Association and subsequently refined through Virmani\u2019s framework. Particular emphasis is placed on plaque instability, highlighting the qualitative features\u2014such as fibrous cap thinning, necrotic core expansion, macrophage-driven inflammation, plaque erosion, and calcification patterns\u2014that determine clinical outcomes rather than luminal stenosis alone. Furthermore, the review discusses the expanding role of immunohistochemical markers in defining plaque biology, including lineage markers and functional indicators of inflammation, matrix integrity, osteogenic signaling, and local anticoagulant balance. These pathological insights are integrated with contemporary risk assessment tools, imaging modalities, preventive strategies, and therapeutic interventions, including emerging lipid-lowering and RNA-based therapies. In conclusion, pathology remains central to understanding atherosclerosis as a biologically active disease and to refining concepts of plaque instability. Integrating histopathology with molecular profiling, imaging, and clinical data is essential for advancing precision prevention and targeted treatment strategies in atherosclerotic cardiovascular disease.<\/jats:p>","DOI":"10.3390\/jcdd13020085","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T14:05:15Z","timestamp":1770645915000},"page":"85","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Atherosclerosis: A Pathologist\u2019s Perspective"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2507-6258","authenticated-orcid":false,"given":"Ludmila","family":"Verboova","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, Rastislavova 43, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-9829","authenticated-orcid":false,"given":"Adam","family":"Nedoroscik","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, Rastislavova 43, 040 11 Ko\u0161ice, Slovakia"},{"name":"The Clinical and Transplant Pathology Centre, Institute of Clinical and Experimental Medicine, 140 21 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-9790","authenticated-orcid":false,"given":"Terezia","family":"Kiskova-Simkova","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, Rastislavova 43, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Smirjakova","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, Rastislavova 43, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bohus","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, Rastislavova 43, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kollar","sequence":"additional","affiliation":[{"name":"The Clinical and Transplant Pathology Centre, Institute of Clinical and Experimental Medicine, 140 21 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Virag","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Faculty of Medicine, East Slovak Institute of Cardiovascular Diseases, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, 040 01 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krist\u00edna","family":"Mazarova","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Faculty of Medicine, East Slovak Institute of Cardiovascular Diseases, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, 040 01 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Zavacka","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Faculty of Medicine, East Slovak Institute of Cardiovascular Diseases, University of Pavol Jozef \u0160af\u00e1rik in Ko\u0161ice, 040 01 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","first-page":"153","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"81","author":"Roth","year":"2023","journal-title":"J. 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