Pathophysiology of Plaque Erosion in Acute Coronary Syndrome: State of the Art
Carlos Olivares Asencio, MD, MSc *
*Correspondence to: Carlos Olivares Asencio, MD, MSc, Universidad de la Frontera. Hospital Hernán Henríquez Aravena Temuco. Chile Cardiologist and Interventional Cardiologist Master in Hemodynamics, Spanish Society of Cardiology (Sociedad Española de Cardiología). Member of the Hemodynamics Council of the Inter-American Society of Cardiology.
© 2026 Carlos Olivares Asencio. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 09 June 2026
Published: 01 July 2026
DOI: https://doi.org/10.5281/zenodo.21095064
Abstract
Background: Plaque erosion represents a distinct pathophysiological mechanism of acute coronary syndrome (ACS), accounting for approximately 33-40% of cases. Unlike plaque rupture, erosion is characterized by endothelial dysfunction, adaptive immune activation, and altered biomechanical forces in the absence of fibrous cap rupture.
Objectives: This state-of-the-art review synthesizes current evidence on the molecular, cellular, and biomechanical mechanisms underlying plaque erosion, its epidemiology, diagnostic approaches, and therapeutic implications.
Methods: Comprehensive review of contemporary literature on plaque erosion pathophysiology, including histopathological studies, intravascular imaging investigations, and clinical trials through 2025.
Results: Plaque erosion exhibits distinct epidemiological patterns, occurring more frequently in younger women and smokers. Histopathologically, it features an intact fibrous cap, lower inflammatory burden, and preserved structural integrity. Key pathophysiological mechanisms include endothelial cell dysfunction with matrix exposure, T lymphocyte-mediated adaptive immunity, high spatial endothelial shear stress gradients, neutrophil extracellular trap (NET) formation, and platelet activation on exposed subendothelial matrix. Optical coherence tomography (OCT) serves as the gold standard for in vivo diagnosis. Patients with plaque erosion demonstrate better prognosis compared to those with plaque rupture, with emerging evidence supporting conservative treatment strategies including intensive antithrombotic therapy without stenting in selected cases.
Conclusions: Recognition of plaque erosion as a distinct entity enables personalized therapeutic approaches. Future research should focus on molecular mechanisms, non-invasive biomarkers, and randomized trials to optimize management and advance precision medicine in ACS.
Abbreviations
ACS = acute coronary syndrome
DAPT = dual antiplatelet therapy
ECM = extracellular matrix
ESS = endothelial shear stress
IVUS = intravascular ultrasound
MMP = matrix metalloproteinase
NET = neutrophil extracellular trap
NSTEMI = non-ST-elevation myocardial infarction
OCT = optical coherence tomography
PCI = percutaneous coronary intervention
STEMI = ST-elevation myocardial infarction
TCFA = thin-cap fibroatheroma
Introduction
The pathophysiology of acute coronary syndrome (ACS) has undergone substantial revision over the past two decades. Historically, plaque rupture was considered the predominant mechanism underlying ACS, with the vulnerable plaque paradigm dominating cardiovascular research and clinical practice [1]. However, advances in intravascular imaging, particularly optical coherence tomography (OCT), have revealed that plaque erosion represents a distinct and clinically significant pathophysiological entity, accounting for approximately one-third to 40% of ACS cases [2], [3], [4], [5].
This paradigm shift has profound implications for understanding ACS mechanisms, risk stratification, and therapeutic strategies. Unlike plaque rupture, which is characterized by disruption of a thin fibrous cap overlying a large necrotic core with abundant inflammatory cells, plaque erosion occurs on plaques with intact fibrous caps and is associated with endothelial dysfunction, altered hemodynamic forces, and distinct immune responses [6], [7], [8].
The recognition of plaque erosion as a separate entity emerged from autopsy studies by Virmani and colleagues, who demonstrated that a substantial proportion of fatal coronary thromboses occurred without fibrous cap rupture [9]. Subsequent in vivo imaging studies using OCT have confirmed these findings and enabled real-time diagnosis of plaque erosion in living patients, fundamentally changing our approach to ACS management [10], [11].
Understanding the pathophysiology of plaque erosion is critical for several reasons. First, patients with plaque erosion demonstrate different demographic and clinical characteristics compared to those with plaque rupture, including younger age, female predominance, and smoking as a major risk factor [12], [13]. Second, the prognosis of patients with plaque erosion is generally more favorable than those with plaque rupture, with lower rates of adverse cardiovascular events [14], [15]. Third, and perhaps most importantly, the distinct mechanisms underlying plaque erosion suggest that alternative therapeutic strategies, including conservative management without stenting in selected cases, may be appropriate [16], [17].
This state-of-the-art review synthesizes current knowledge on the pathophysiology of plaque erosion, examining its epidemiology, histopathological characteristics, molecular and cellular mechanisms, diagnostic approaches, and therapeutic implications. We aim to provide a comprehensive framework for understanding this important ACS mechanism and to highlight areas requiring further investigation to advance precision medicine in cardiovascular care.
Epidemiology and Prevalance
The reported prevalence of plaque erosion in ACS varies depending on the population studied, diagnostic methods employed, and clinical presentation. Contemporary studies using OCT have demonstrated that plaque erosion accounts for 25-40% of ACS cases, with the highest rates observed in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) or unstable angina [2], [18], [19]. In contrast, plaque rupture remains the predominant mechanism in ST-elevation myocardial infarction (STEMI), particularly in older patients with extensive atherosclerotic disease [20].
A landmark OCT study by Jang and colleagues found that among 126 patients with ACS, 44% had plaque rupture, 31% had plaque erosion, and 8% had calcified nodules, with the remaining cases showing no definite culprit lesion [21]. Subsequent larger studies have confirmed these proportions, with plaque erosion consistently representing approximately one-third of ACS cases when assessed by high-resolution intravascular imaging [22], [23].
Geographic and ethnic variations in plaque erosion prevalence have been reported, with some Asian populations demonstrating higher rates of erosion compared to Western cohorts [24]. These differences may reflect genetic factors, environmental influences, or variations in traditional cardiovascular risk factor profiles across populations [25].
Plaque erosion exhibits distinct demographic patterns that differentiate it from plaque rupture. Multiple studies have consistently demonstrated that plaque erosion occurs more frequently in younger patients, with a mean age approximately 5-10 years younger than those with plaque rupture [12], [26], [27]. This age difference has important implications for risk stratification and preventive strategies in younger populations.
Gender represents another critical demographic factor, with plaque erosion showing a marked female predominance. Women account for 40-60% of plaque erosion cases, compared to only 20-30% of plaque rupture cases [13], [28], [29].
This gender disparity is particularly pronounced in premenopausal women, suggesting potential roles for hormonal factors and sex-specific differences in endothelial function and vascular biology [30].
Smoking emerges as the most consistently associated risk factor for plaque erosion, with active smoking present in 70-80% of cases [31], [32]. The strong association between smoking and plaque erosion likely reflects the direct toxic effects of cigarette smoke on endothelial cells, including increased oxidative stress, impaired endothelial repair mechanisms, and enhanced thrombogenicity [33]. In contrast, traditional risk factors such as hypertension, hyperlipidemia, and diabetes mellitus show weaker associations with plaque erosion compared to plaque rupture [34].
Patients with plaque erosion typically present with less severe clinical manifestations compared to those with plaque rupture. NSTEMI and unstable angina are more common presentations, while STEMI occurs less frequently [35]. Cardiac biomarker elevations tend to be lower in plaque erosion, reflecting smaller areas of myocardial necrosis and less extensive thrombotic burden [36].
Importantly, the prognosis of patients with plaque erosion is significantly better than those with plaque rupture. Multiple studies have demonstrated lower rates of major adverse cardiovascular events (MACE), including death, recurrent myocardial infarction, and target vessel revascularization, in patients with erosion [14], [37], [38]. This favorable prognosis persists even after adjustment for baseline clinical characteristics and treatment strategies, suggesting that the underlying pathophysiology of erosion confers inherent prognostic advantages [39].
The better outcomes associated with plaque erosion may reflect several factors, including smaller thrombus burden, less extensive myocardial damage, lower inflammatory burden, and potentially greater responsiveness to antithrombotic therapy [40]. These prognostic differences have important implications for risk stratification and may support less aggressive interventional strategies in selected patients with plaque erosion [41].
Histopathological Characteristics
Plaque erosion is defined histopathologically by the presence of luminal thrombus in direct contact with the intima in the absence of fibrous cap rupture [9], [42]. This fundamental distinction from plaque rupture has been established through extensive autopsy studies and validated by in vivo imaging [43]. The fibrous cap in eroded plaques remains intact, often measuring thicker than the 65-μm threshold that defines thin-cap fibroatheromas (TCFA) [44].
The endothelial layer overlying eroded plaques shows focal or extensive denudation, with loss of endothelial cell coverage exposing the underlying subendothelial matrix to circulating blood [45]. This endothelial disruption creates a thrombogenic surface that promotes platelet adhesion and activation, initiating the thrombotic cascade without requiring fibrous cap rupture [46].
Thrombus composition in plaque erosion differs from that in plaque rupture. Eroded plaques typically feature platelet-rich white thrombi, reflecting primary platelet activation on exposed matrix components, whereas ruptured plaques more commonly show mixed thrombi with greater fibrin and red blood cell content [47]. This compositional difference has implications for thrombus resolution and response to antithrombotic therapy [48].
The underlying plaque architecture in erosion cases differs substantially from that of rupture-prone lesions. Eroded plaques generally contain smaller lipid cores or may lack a distinct necrotic core entirely [49]. When present, the lipid core is typically separated from the lumen by a thick, intact fibrous cap rich in smooth muscle cells and collagen [50].
The extracellular matrix (ECM) composition of eroded plaques shows distinctive features, with abundant proteoglycans, particularly hyaluronan and versican, in the superficial intima [51]. These proteoglycans may contribute to plaque erosion through multiple mechanisms, including water retention leading to tissue edema, disruption of endothelial-matrix interactions, and modulation of inflammatory responses [52].
Smooth muscle cell content in eroded plaques is generally higher than in ruptured plaques, with these cells often showing a synthetic phenotype characterized by increased ECM production [53]. The preservation of smooth muscle cells may contribute to the structural stability of eroded plaques and their intact fibrous caps [54].
A hallmark feature of plaque erosion is its relatively low inflammatory burden compared to plaque rupture. Eroded plaques contain fewer macrophages, particularly in the superficial intima where erosion occurs [55]. The macrophages present in eroded plaques may exhibit different phenotypes, with some studies suggesting a predominance of M2-like alternatively activated macrophages rather than the M1 pro-inflammatory phenotypes characteristic of ruptured plaques [56].
T lymphocytes, particularly CD4+ T cells, are present in eroded plaques and may play important pathophysiological roles despite the overall lower inflammatory burden [57]. Recent studies have highlighted the potential importance of adaptive immunity and specific T cell subsets in plaque erosion, as discussed in detail in subsequent sections [58].
Neutrophil infiltration in eroded plaques has received increasing attention, particularly regarding the formation of neutrophil extracellular traps (NETs) [59]. While neutrophil numbers may not be dramatically elevated compared to ruptured plaques, their activation state and NET formation appear to play critical roles in erosion pathophysiology [60].
Eroded plaques often demonstrate positive remodeling, with outward expansion of the vessel wall to accommodate plaque growth while preserving luminal dimensions [61]. This remodeling pattern differs from the negative remodeling sometimes observed in ruptured plaques and may reflect differences in inflammatory mediators and matrix remodeling processes [62].
The adventitia and vasa vasorum in vessels with eroded plaques show less extensive neovascularization compared to ruptured plaques [63]. This difference may contribute to the lower inflammatory burden in erosion, as neovessels serve as conduits for inflammatory cell recruitment and may be sources of intraplaque hemorrhage [64].
Pathophysiological Mechanisms
Endothelial dysfunction represents the central pathophysiological mechanism underlying plaque erosion [65]. The endothelium normally provides a protective barrier between circulating blood and the vessel wall, maintaining vascular homeostasis through multiple functions including regulation of vascular tone, prevention of thrombosis, and control of inflammatory cell recruitment [66].
In plaque erosion, endothelial cells undergo dysfunction and detachment, exposing the thrombogenic subendothelial matrix [67]. This process involves multiple mechanisms, including increased endothelial cell apoptosis, impaired cell-cell and cell-matrix adhesion, and altered endothelial cell phenotype [68]. The glycocalyx, a carbohydrate-rich layer on the endothelial surface that normally provides antithrombotic properties, becomes disrupted in areas of erosion, further promoting thrombosis [69].
Molecular mechanisms of endothelial dysfunction in erosion include dysregulation of key transcription factors such as Krüppel-like factors (KLFs), particularly KLF2 and KLF4, which normally maintain endothelial homeostasis and atheroprotective gene expression [70]. Loss of these protective factors leads to increased expression of pro-inflammatory and pro-thrombotic genes [71].
Oxidative stress plays a critical role in endothelial dysfunction associated with plaque erosion. Reactive oxygen species (ROS) generated by various sources, including NADPH oxidases, mitochondria, and uncoupled endothelial nitric oxide synthase (eNOS), damage endothelial cells and impair their function [72]. Smoking, the major risk factor for plaque erosion, is a potent inducer of oxidative stress and directly damages endothelial cells [73].
Endothelial-to-mesenchymal transition (EndMT) has emerged as a potential mechanism contributing to endothelial dysfunction in atherosclerosis [74]. During EndMT, endothelial cells lose their characteristic markers and acquire mesenchymal features, potentially contributing to plaque instability and erosion [75].
While plaque erosion is characterized by lower overall inflammatory burden compared to rupture, specific immune mechanisms play critical roles in its pathophysiology. Recent research has highlighted the importance of adaptive immunity, particularly T lymphocyte responses, in plaque erosion [58], [76].
CD4+ T cells, especially T helper (Th) cell subsets, are present in eroded plaques and contribute to local inflammatory responses [77]. Th1 cells produce interferon-gamma (IFN-γ), which can impair endothelial function and promote endothelial cell apoptosis [78]. Th17 cells, which produce interleukin-17 (IL-17), may also contribute to erosion through effects on endothelial cells and matrix remodeling [79].
Regulatory T cells (Tregs), which normally suppress inflammatory responses and promote plaque stability, may be dysfunctional or reduced in number in areas of erosion [80]. Loss of Treg-mediated immunosuppression could contribute to endothelial dysfunction and erosion development [81].
The role of innate immunity in plaque erosion differs from that in rupture. While macrophage numbers are lower in eroded plaques, those present may contribute to erosion through production of matrix metalloproteinases (MMPs) and other factors that degrade the ECM and impair endothelial-matrix interactions [82]. Mast cells, which are present in atherosclerotic plaques, can release proteases and inflammatory mediators that may contribute to endothelial dysfunction and erosion [83].
Cytokine profiles in plaque erosion differ from those in rupture, with some studies suggesting lower levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) [84]. However, specific cytokines and chemokines involved in endothelial dysfunction and T cell recruitment may be elevated in erosion [85].
Hemodynamic forces, particularly endothelial shear stress (ESS), play crucial roles in plaque erosion pathophysiology [86]. ESS represents the frictional force exerted by flowing blood on the endothelial surface and profoundly influences endothelial cell function, gene expression, and phenotype [87].
High ESS and, more importantly, high spatial ESS gradients have been identified as independent predictors of plaque erosion sites [88]. Computational fluid dynamics studies combined with intravascular imaging have demonstrated that areas of erosion frequently occur at sites of elevated ESS and rapid spatial changes in ESS [89]. These biomechanical forces can induce endothelial dysfunction, promote endothelial cell detachment, and create a pro-thrombotic environment [90].
The mechanisms by which high ESS contributes to erosion involve mechanotransduction pathways that convert mechanical forces into biochemical signals [91]. High ESS can activate endothelial cell signaling cascades that promote inflammation, increase oxidative stress, and impair endothelial barrier function [92]. Conversely, physiological laminar shear stress is generally atheroprotective, promoting endothelial alignment, quiescence, and expression of protective genes [93].
Oscillatory shear stress and disturbed flow patterns, which occur at arterial bifurcations and areas of vessel curvature, may also contribute to erosion by promoting endothelial dysfunction and inflammatory activation [94]. These flow patterns are associated with increased endothelial cell turnover, impaired cell-cell junctions, and enhanced permeability [95].
The interaction between biomechanical forces and biological factors is complex and bidirectional. Plaque composition and geometry influence local hemodynamics, while hemodynamic forces modulate plaque biology and stability [96]. This interplay is particularly relevant in plaque erosion, where structural features such as proteoglycan-rich matrix may alter local flow patterns and ESS distribution [97].
Neutrophil extracellular traps (NETs) have emerged as important mediators of thrombosis in plaque erosion [98]. NETs are web-like structures composed of decondensed chromatin decorated with histones and antimicrobial proteins that neutrophils release in response to various stimuli through a process called NETosis [99].
In the context of plaque erosion, NETs contribute to thrombosis through multiple mechanisms. The DNA scaffold of NETs provides a surface for platelet adhesion and activation, while NET-associated histones are directly cytotoxic to endothelial cells and promote platelet aggregation [100].
NETs also activate the coagulation cascade through multiple pathways, including providing a surface for thrombin generation and directly activating factor XII [101].
Evidence for NET involvement in plaque erosion comes from both autopsy studies and in vivo investigations. Immunohistochemical analyses have demonstrated the presence of NET markers, including citrullinated histone H3 and myeloperoxidase-DNA complexes, in eroded plaques [102]. Circulating NET markers are elevated in patients with ACS due to erosion compared to stable coronary disease [103].
The triggers for NET formation in plaque erosion are multifactorial. Endothelial dysfunction and damage expose subendothelial matrix components that can activate neutrophils [104]. Platelets activated on the eroded surface release factors that promote NET formation [105]. Inflammatory mediators present in the plaque microenvironment, including cytokines and chemokines, can also induce NETosis [106].
Smoking, the major risk factor for plaque erosion, is a potent inducer of NET formation [107]. Cigarette smoke components activate neutrophils and promote NETosis through oxidative stress and direct cellular effects [108]. This mechanism may partially explain the strong association between smoking and plaque erosion [109].
The role of NETs in plaque erosion extends beyond acute thrombosis. NETs may contribute to endothelial dysfunction and damage, creating a feed-forward cycle that promotes erosion progression [110]. NET-associated proteases can degrade the ECM and impair endothelial-matrix interactions [111]. Additionally, NETs may modulate immune responses in the plaque microenvironment [112].
Platelet activation and aggregation are central to thrombus formation in plaque erosion [113]. Unlike plaque rupture, where thrombus formation is triggered by exposure of highly thrombogenic necrotic core contents, erosion-associated thrombosis results from platelet activation on exposed subendothelial matrix components [114].
The subendothelial matrix exposed in plaque erosion contains multiple platelet agonists, including collagen, von Willebrand factor (vWF), fibronectin, and laminin [115]. Platelets adhere to these matrix components through specific receptors, including glycoprotein (GP) Ia/IIa (α2β1 integrin) for collagen, GPIb-IX-V complex for vWF, and GPIIb/IIIa (αIIbβ3 integrin) for multiple ligands [116].
Following adhesion, platelets undergo activation, characterized by shape change, granule secretion, and expression of activated GPIIb/IIIa receptors that mediate platelet aggregation [117]. Activated platelets release the contents of their granules, including adenosine diphosphate (ADP), thromboxane A2, and various growth factors and chemokines that amplify platelet activation and recruit additional platelets [118].
The composition of thrombi in plaque erosion reflects the primary role of platelet activation, with predominance of platelet-rich white thrombi [119]. This contrasts with the mixed thrombi containing more fibrin and red blood cells typically seen in plaque rupture [120]. The platelet-rich nature of erosion-associated thrombi has implications for treatment, potentially explaining the effectiveness of antiplatelet therapy in these patients [121].
Interactions between platelets and other blood cells contribute to thrombosis in erosion. Platelet-neutrophil interactions promote NET formation, while platelet-monocyte aggregates enhance inflammatory responses [122]. These cellular interactions create a pro-thrombotic and pro-inflammatory microenvironment at erosion sites [123].
Platelet activation in erosion may be modulated by endothelial-derived factors. Dysfunctional endothelium produces less nitric oxide and prostacyclin, both of which normally inhibit platelet activation [124]. Loss of these protective factors enhances platelet reactivity and promotes thrombosis [125].
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