Influence of Microcalcifications on Stress Development Within a Vulnerable Plaque’s Cap

2011 ◽  
Author(s):  
Ze’ev Aronis ◽  
Erez Kanka ◽  
Eyass Massarwa ◽  
Rami Haj-Ali ◽  
Shmuel Einav
Keyword(s):  
Mechanical Characteristics ◽  
Plaque Rupture ◽  
Intraplaque Hemorrhage ◽  
Rapid Progression ◽  
Stress Concentrations ◽  
Coronary Syndrome ◽  
Vulnerable Plaques ◽  
Material Fatigue ◽  
Mechanical Factors ◽  
As Stress

Vulnerable plaques are inflamed, active, and growing lesions which are prone to complications such as rupture, luminal and mural thrombosis, intraplaque hemorrhage, and rapid progression to stenosis. Despite major advances in the prevention and treatment of this disease, it remains the leading cause of morbidity and mortality worldwide, accounting for 30% of all deaths globally [1]. The importance of stress/strain distribution is now well recognized in vascular pathophysiology, specifically in the mechanisms of plaque rupture. Finite element modeling (FEM) and advanced fluid structure interaction (FSI) studies can better characterize coronary stenosis coupling constitutive equations. Mechanical factors such as stress concentrations within a plaque (material fatigue), lesion characteristic (location, size, and composition), and flow patterns are involved in rupture of plaques. Assessment of local mechanical characteristics caused by plaque structure is important for identifying vulnerable plaques and may improve final estimation of the risk for coronary syndrome.

Stress Concentrations of Vulnerable Plaques With a Composite Variable Core

2010 ◽  
Author(s):  
Eyass Massarwa ◽  
Aronis Ze’ev ◽  
Rami Eliasy ◽  
Rami Haj-Ali ◽  
Shmuel Einav
Keyword(s):  
Plaque Rupture ◽  
Necrotic Core ◽  
Intraplaque Hemorrhage ◽  
Plaque Morphology ◽  
Rapid Progression ◽  
Stress Concentrations ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Vulnerable Plaques ◽  
Life Threatening

Vulnerable plaques are inflamed, active, and growing lesions which are prone to complications such as rupture, luminal and mural thrombosis, intraplaque hemorrhage, and rapid progression to stenosis. It remains difficult to assess what factors influence the biomechanical stability of vulnerable plaques and promote some of them to rupture while others remain intact. The rupture of thin fibrous cap overlying the necrotic core of a vulnerable plaque is the principal cause of acute coronary syndrome. The mechanism or mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to a life threatening athero-thrombotic lesion are not fully understood. It has been widely assumed that plaque morphology is the major determinant of clinical outcome [1, 2]. Thin-cap fibroatheroma with a large necrotic core and a fibrous cap of < 65μm was describes as a more specific precursor of plaque rupture due to tissue stress.

scholarly journals Optical Coherence Tomography Imaging in Acute Coronary Syndromes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takashi Kubo ◽  
Yasushi Ino ◽  
Takashi Tanimoto ◽  
Hironori Kitabata ◽  
Atsushi Tanaka ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
High Resolution ◽  
Acute Coronary Syndromes ◽  
Plaque Rupture ◽  
Vasa Vasorum ◽  
Optical Coherence ◽  
Coronary Syndrome ◽  
Vulnerable Plaques ◽  
Coronary Syndromes

Optical coherence tomography (OCT) is a high-resolution imaging technique that offers microscopic visualization of coronary plaques. The clear and detailed images of OCT generate an intense interest in adopting this technique for both clinical and research purposes. Recent studies have shown that OCT is useful for the assessment of coronary atherosclerotic plaques, in particular the assessment of plaque rupture, erosion, and intracoronary thrombus in patients with acute coronary syndrome. In addition, OCT may enable identifying thin-cap fibroatheroma, the proliferation of vasa vasorum, and the distribution of macrophages surrounding vulnerable plaques. With its ability to view atherosclerotic lesions in vivo with such high resolution, OCT provides cardiologists with the tool they need to better understand the thrombosis-prone vulnerable plaques and acute coronary syndromes. This paper reviews the possibility of OCT for identification of vulnerable plaques in vivo.

scholarly journals Protective Functions of Liver X Receptor α in Established Vulnerable Plaques: Involvement of Regulating Endoplasmic Reticulum–Mediated Macrophage Apoptosis and Efferocytosis

2021 ◽  
Author(s):  
Xinyu Che ◽  
Qingqing Xiao ◽  
Wei Song ◽  
Hengyuan Zhang ◽  
Beibei Sun ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Apolipoprotein E ◽  
Plaque Rupture ◽  
Liver X Receptor ◽  
Intraplaque Hemorrhage ◽  
Vehicle Group ◽  
Lesion Volume ◽  
Genetic Ablation ◽  
Vulnerable Plaques

Background Liver X receptor (LXR) belongs to the metabolic nuclear receptor superfamily, which plays a critical regulatory role in vascular physiology/pathology. However, effects of systemic LXR activation on established vulnerable plaques and the potential isotype‐specific role involved remain unclear. Methods and Results The 8‐week‐old male apolipoprotein E −/− mice went through carotid branch ligation and renal artery constriction, combined with a high‐fat diet. Plaques in the left carotid artery acquired vulnerable features 4 weeks later, confirmed by magnetic resonance imaging scans and histological analysis. From that time on, mice were injected intraperitoneally daily with PBS or GW3965 (10 mg/kg per day) for an additional 4 weeks. Treatment with LXR agonists reduced the lesion volume by 52.61%, compared with the vehicle group. More important, a profile of less intraplaque hemorrhage detection and necrotic core formation was found. These actions collectively attenuated the incidence of plaque rupture. Mechanistically, reduced lesional apoptosis, enhanced efferocytosis, and alleviated endoplasmic reticulum stress are involved in the process. Furthermore, genetic ablation of LXRα, but not LXRβ, blunted the protective effects of LXR on the endoplasmic reticulum stress–elicited C/EBP‐homologous protein pathway in peritoneal macrophages. In concert with the LXRα‐predominant role in vitro, activated LXR failed to stabilize vulnerable plaques and correct the acquired cellular anomalies in LXRα −/− apolipoprotein E −/− mice. Conclusions Our results revealed that LXRα mediates the capacity of LXR activation to stabilize vulnerable plaques and prevent plaque rupture via amelioration of macrophage endoplasmic reticulum stress, lesional apoptosis, and defective efferocytosis. These findings might expand the application scenarios of LXR therapeutics for atherosclerosis.

scholarly journals Plaque Erosion: A Distinctive Pathological Mechanism of Acute Coronary Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Xing Luo ◽  
Ying Lv ◽  
Xiaoxuan Bai ◽  
Jinyu Qi ◽  
Xiuzhu Weng ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Outcomes ◽  
Plaque Rupture ◽  
Accurate Diagnosis ◽  
Coronary Syndrome ◽  
Pathological Characteristics ◽  
Vulnerable Plaques ◽  
Plaque Erosion ◽  
Pathological Mechanism ◽  
Clinical Strategies

Plaque erosion (PE) is one of the most important pathological mechanisms underlying acute coronary syndrome (ACS). The incidence of PE is being increasingly recognized owing to the development and popularization of intracavitary imaging. Unlike traditional vulnerable plaques, eroded plaques have unique pathological characteristics. Moreover, recent studies have revealed that there are differences in the physiopathological mechanisms, biomarkers, and clinical outcomes between PE and plaque rupture (PR). Accurate diagnosis and treatment of eroded plaques require an understanding of the pathogenesis of PE. In this review, we summarize recent scientific discoveries of the pathological characteristics, mechanisms, biomarkers, clinical strategies, and prognosis in patients with PE.

Analysis of Biomechanical Forces Influencing Atherosclerotic Plaque Vulnerability

2009 ◽  
Author(s):  
Ze’ev Aronis ◽  
Shmuel Einav
Keyword(s):  
Atherosclerotic Plaque ◽  
Intraplaque Hemorrhage ◽  
Western World ◽  
Plaque Morphology ◽  
Rapid Progression ◽  
Heart Attacks ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Life Threatening ◽  
Biomechanical Forces

Cardiovascular disease has long been the leading cause of death in the western world: over 1.4 million heart attacks are suffered every year, more than half of which prove fatal. Vulnerable plaques are inflamed, active, and growing lesions which are prone to complications such as rupture, luminal and mural thrombosis, intraplaque hemorrhage, and rapid progression to stenosis. The rupture of thin fibrous cap overlying the necrotic core of a vulnerable plaque is the principal cause of acute coronary syndrome. The mechanism or mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to a life threatening athero-thrombotic lesion are not fully understood. It has been widely assumed that plaque morphology is the major determinant of clinical outcome [1, 2].

Classification of Vulnerable Plaques in Human Coronary Arteries Using High Resolution Micro-CT Imaging

2011 ◽  
Author(s):  
Adreanne Kelly ◽  
Natalia Maldonado ◽  
Yuliya Vengrenyuk ◽  
John T. Fallon ◽  
Renu Virmani ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
High Resolution ◽  
Coronary Arteries ◽  
Plaque Rupture ◽  
Ct Imaging ◽  
Micro Ct ◽  
Coronary Syndrome ◽  
Vulnerable Plaques ◽  
Risk Of Rupture

Sixty percent of the more than 500,000 cases of acute coronary syndrome that lead to death are due to plaque rupture. Understanding the mechanisms of rupture is important to predicting the risk of rupture. Determining these mechanisms begins with acquiring an accurate visualization of the arteries containing fiberoatherotic lesions or fibroatheroma.

The Role of Angiogenesis in Coronary Artery Disease: A Double-Edged Sword: Intraplaque Angiogenesis in Physiopathology and Therapeutic Angiogenesis for Treatment

2018 ◽  
Vol 24 (4) ◽  
pp. 451-464 ◽  
Author(s):  
Wen Wu ◽  
Xiaobo Li ◽  
Guangfeng Zuo ◽  
Jiangqin Pu ◽  
Xinlei Wu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Plaque Rupture ◽  
Therapeutic Angiogenesis ◽  
Intraplaque Hemorrhage ◽  
Protein Therapy ◽  
Angiogenic Growth Factors ◽  
Coronary Syndrome ◽  
Artery Disease

Angiogenesis is described as a sprouting and growth process of new blood vessels from pre-existing vasculature. The relationship between angiogenesis and coronary artery disease (CAD) is double-sided. On one hand, angiogenesis within plaques is responsible for facilitating the growth and vulnerability of plaques by causing intraplaque hemorrhage and inflammatory cell influx, and overabundance of erythrocytes and inflammatory cells within a plaque probably causes plaque rupture, further leading to acute coronary syndrome. Therefore, inhibiting intraplaque angiogenesis has been considered as a potential therapeutic target for CAD. On the other hand, aiming at improving reperfusion to the ischemic myocardium in patients with CAD, angiogenesis promoting has been utilized as a therapeutic approach to expand myocardial microvascular network. Current strategies include direct administration of angiogenic growth factors (protein therapy), promoting angiogenic genes expression in vivo (gene therapy), and delivering stem cells (cell therapy) or exosomes (cell free therapy). This article will start by clarifying the basic concept of angiogenesis, interpret the mechanism of excessive intraplaque angiogenesis in atherosclerosis, and discuss its role in the growth and vulnerability of plaques. Then we will focus on the four distinct strategies of therapeutic angiogenesis. Despite promising animal studies and smallscale clinical trials of therapeutic angiogenesis in patients with ischemic heart disease, investigations have far not shown definite evidence of clinical efficacy. Hence, while acknowledging future work that remains to be done to validate the clinical results, we reviewed the critical challenges in this arena and highlighted the exciting progress that has occurred recently.

Association between apolipoprotein B/A1 ratio and coronary plaque vulnerability in patients with atherosclerotic cardiovascular disease: an intravascular optical coherence tomography study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fuxue Deng ◽  
Danni Li ◽  
Lei Lei ◽  
Qiang Yang ◽  
Qing Li ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Optical Coherence Tomography ◽  
Logistic Regression ◽  
Roc Curve ◽  
Plaque Rupture ◽  
Atherosclerotic Cardiovascular Disease ◽  
Apo B ◽  
Coronary Syndrome ◽  
Vulnerable Plaques ◽  
Intravascular Optical Coherence Tomography

Abstract Background Apolipoprotein (Apo) A1 and Apo B are strongly associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the relationship between the Apo B/A1 ratio and the morphology of coronary vulnerable plaques has not been fully elucidated in patients with ASCVD. Methods A total of 320 patients with ASCVD undergoing percutaneous coronary intervention were enrolled and assigned into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) group. The morphology of culprit plaque was analyzed by intravascular optical coherence tomography. Association between the Apo B/A1 ratio and coronary vulnerable plaques were evaluated using logistic regression models and receiver operator characteristic (ROC) curve analyses. Results The Apo B/A1 ratio was higher in ACS patients than CCS patients (0.77 ± 0.28 vs. 0.64 ± 0.22, P < 0.001) and it was also higher in patients with plaque rupture, erosion or thrombus than those without culprit plaques. The high Apo B/A1 ratio was associated with high percent of vulnerable plaques compared with low ratio group. The Apo B/A1 ratio was negatively related to fibrous cap thickness in lipid-rich plaque (r = − 0.228, P = 0.043). Univariate and multivariate logistic regression analyses revealed that the Apo B/A1 ratio was an independent factor of plaque rupture, erosion, and thrombus. The area under the ROC curve of the Apo B/A1 ratio for plaque rupture, erosion, and thrombus were 0.632, 0.624, and 0.670 respectively (P < 0.001 for all), which were higher than that of low-density lipoprotein cholesterol. Conclusions The Apo B/A1 ratio is an independent predictor for plaque rupture, erosion, and thrombus in patients with ASCVD.

scholarly journals Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque

2021 ◽  
Vol 8 ◽  
Author(s):  
Xueyu Wang ◽  
Yahong Fu ◽  
Zulong Xie ◽  
Muhua Cao ◽  
Wenbo Qu ◽  
...  
Keyword(s):  
Vulnerable Plaque ◽  
Plaque Rupture ◽  
Fold Increase ◽  
Cell Number ◽  
Intraplaque Hemorrhage ◽  
Aortic Sinus ◽  
Coronary Syndrome ◽  
Atherosclerotic Lesions ◽  
Unstable Plaques ◽  
Novel Model

Background and Aims: Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.Methods: Fbn1C1039G+/− mice were crossbred with LDLR−/− mice to obtain a novel model for atherosclerotic VP. After the mice were fed with a high-fat diet (HFD) for 12 or 24 weeks, pathological staining and immunohistochemistry analyses were employed to evaluate atherosclerotic lesions.Results: Compared to control mice, Fbn1C1039G+/−LDLR−/− mice developed more severe atherosclerotic lesions, and the positive area of oil red O staining in the aortic sinus was significantly increased after 12 weeks (21.7 ± 2.0 vs. 6.3 ± 2.1) and 24 weeks (32.6 ± 2.5 vs. 18.7 ± 2.6) on a HFD. Additional vulnerable plaque characteristics, including significantly larger necrotic cores (280 ± 19 vs. 105 ± 7), thinner fiber caps (14.0 ± 2.8 vs. 32.6 ± 2.7), apparent elastin fiber fragmentation and vessel dilation (3,010 ± 67 vs. 1,465 ± 49), a 2-fold increase in macrophage number (8.5 ± 1.0 vs. 5.0 ± 0.6), obviously decreased smooth muscle cell number (0.6 ± 0.1 vs. 2.1 ± 0.2) and an ~25% decrease in total collagen content (33.6 ± 0.3 vs. 44.9 ± 9.1) were observed in Fbn1C1039G+/−LDLR−/− mice compared with control mice after 24 weeks. Furthermore, spontaneous plaque rupture, neovascularization, and intraplaque hemorrhage were detected in the model mouse plaque regions but not in those of the control mice.Conclusions: Plaques in Fbn1C1039G+/−LDLR−/− mice fed a HFD show many features of human advanced atherosclerotic unstable plaques. These results suggest that the Fbn1C1039G+/−LDLR−/− mouse is a novel model for investigating the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques.

Macrophage infiltrates in coronary plaque erosion portend a worse cardiovascular outcome in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
V Vetrugno ◽  
M Camilli ◽  
M Russo ◽  
M.G Del Buono ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Vulnerable Plaque ◽  
Cardiac Death ◽  
Cox Regression ◽  
Plaque Rupture ◽  
Culprit Lesion ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Plaque Erosion

Abstract Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p&lt;0.001], higher prevalence of thrombus [41 (80.4%) vs. 64 (62.7%), p=0.028], lipid plaque [39 (76.5%) vs. 50 (49.0%), p&lt;0.001], TCFA [20 (39.2%) vs. 14 (13.7%), p=0.001], and a higher maximum lipid arc [median [IQR] 250.0° (177.5°-290.0°) vs. 190.0° (150.0°-260.0°), p=0.018) at the culprit lesion compared with PE without MØI. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p=0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression model, PE with MØI [HR=2.95, 95% CI (1.09–8.02), p=0.034] was an independent predictor of MACEs. Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None

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