Cholesterol crystal embolization following plaque rupture： a systemic disease with unusual features

Cholesterol crystal embolic （CCE） syndrome is often a clinically challenging condition that has a poor prognostic implication. It is a result of plaque rupture with release of cholesterol crystals into the circulation that embolize into various tissue organs. Plaque rupture seems to be triggered by an expanding necrotic core during cholesterol crystallization forming sharp tipped crystals that perforate and tear the fibrous cap. Embolizing cholesterol crystals then initiate both local and systemic inflammation that eventually lead to vascular fibrosis and obstruction causing symptoms that can mimic other vasculitic conditions. In fact, animal studies have demonstrated that cholesterol crystals can trigger an inflammatory response via NLRP3 inflammasome similar to that seen with gout. The diagnosis of CCE syndrome often requires a high suspicion of the condition. Serum inflammation biomarkers including elevated sedimentation rate, abnormal renal function tests and eosinophilia are useful but non-specific. Common target organ involvement includes the skin, kidney, and brain. Various testing including fundoscopic eye examination and other non-invasive procedures such as trans-esophageal echocardiography and magnetic resonance imaging may be helpful in identifying the embolic source. Treatment includes aspirin and clopidogrel, high dose statin and possibly steroids. In rare cases, mechanical intervention using covered stents may help isolate the ruptured plaque. Anticoagulation with warfarin is not recommended and might even be harmful. Overall, CCE syndrome is usually a harbinger of extensive and unstable atherosclerotic disease that is often associated with acute cardiovascular events.

Numerical study of biomechanical characteristics of plaque rupture at stenosed carotid bifurcation:a stenosis mechanical property-specific guide for blood pressure control in daily activities

Acute stress concentration plays an important role in plaque rupture and may cause stroke or myocardial infarction.Quantitative evaluation of the relation between in vivo plaque stress and variations in blood pressure and flow rates is valuable to optimize daily monitoring of the cardiovascular system for high-risk patients as well as to set a safe physical exercise intensity for better quality of life.In this study,we constructed an in vivo stress model for a human carotid bifurcation with atherosclerotic plaque,and analyzed the effects of blood pressure,flow rates,plaque stiffness,and stenosis on the elastic stress and fluid viscous stress around the plaque.According to the maximum values of the mechanical stress,we define a risk index to predict the risk level of plaque rupture under different exercise intensities.For a carotid bifurcation where the blood flow divides,the results suggest that the stenosis ratio determines the ratio of the contributions of elastic shear stress and viscous shear stress to plaque rupture.A n increase of the plaque stiffness enhances the maximum elastic shear stress in the plaque,indicating that a high-stiffness plaque is more prone to rupture for given stenosis ratio.High stress co-localization at the shoulder of plaques agrees with the region of plaque injury in clinical observations.It is demonstrated that,due to the stress-shield effect,the rupture risk of a high-stiffness plaque tends to decrease under high-stenosis conditions,suggesting the existence of a specific stenosis corresponding to the maximum risk.This study may help to complement risk stratification of vulnerable plaques in clinical practice and provides a stenosis mechanical property-specific guide for blood pressure control in cardiovascular health management.

Thrombosis and morphology of plaque rupture using optical coherence tomography

Background Thrombosis following plaque rupture is the main cause of acute coronary syndrome, but not all plaque ruptures lead to thrombosis. There are limited in vivo data on the relationship between the morphology of ruptured plaque and thrombosis. Methods We used optical coherence tomography （OCT） to investigate the morphology of plaque rupture and its relation to coronary artery thrombosis in patients with coronary heart disease. Forty-two patients with coronary artery plaque rupture detected by OCT were divided into two groups （with or without thrombus） and the morphological characteristics of ruptured plaque, including fibrous cap thickness and broken cap site, were recorded. Results The fibrous cap of ruptured plaque with thrombus was significantly thinner compared to caps without thrombus （（57.00＋17.00） Bm vs. （96.00＋48.00） Bm; P=0.0076）. Conclusions Plaque rupture associated with thrombosis occurs primarily in plaque covered by a thin fibrous cap. Thick fibrous caps are associated with greater stability of ruptured plaque.

Coronary spasm, a pathogenic trigger of vulnerable plaque rupture

Objective This coronary artery spasm review aimed to explore the most possible pathogenic trigger mechanism of vulnerable plaque rupture. Data sources Data used in this coronary artery spasm review were mainly from Medline and Pubmed in English. Study selection These reports from major review on coronary artery spasm .and these research included coronary artery conception, pathogenesis of spasm, mechanisms of plaque rupture, epidemiological evidence, clinical manifestation and the relationship between coronary artery spasm and vulnerable plaque rupture. Results Coronary artery spasm is somehow related to the presence of atherosclerotic intima disease in the coronary artery. However, chronic low-grade inflammation causes coronary vessel smooth muscle cell hypersensitivity, which can directely cause coronary artery spasm. Myocardial infarction and sudden cardiac death may be initiated by a sudden intense localized contraction of coronary artery smooth muscle. Conclusion Coronary artery spasm may be one trigger that can initiate and exacerbate vulnerable plaque rupture.

The Effect of Carotid Plaque Morphology on Longitudinal Fibrous Cap Stress Levels

Background and Purpose: Rupture of vulnerable carotid atherosclerotic plaques is a major cause of stroke. Stress levels may reflect risk of rupture in patients with carotid atherosclerotic plaques. Features thought to influence the risk of plaque rupture include the degree of stenosis, lipid-rich necrotic core (LR-NC) size, and thickness of the protective fibrous caps. We used computational models to investigate the effect of these variables on fibrous cap stress levels. Methods: Two-way coupled fluid-structure interaction longitudinal 2D simulations were performed on a bifurcation model based on idealized geometry derived from a symptomatic patient. Models with varying degrees of stenosis (50%-95%), fibrous cap thicknesses (0.05-1 mm), and LR-NC sizes (2 × 1 mm-6 × 3 mm) were simulated. The stress distribution for each model was calculated and peak principal stresses extracted. Regression analysis was used for assessing the relationship between the variables and stress levels. Results: Mechanical stresses increased with decreasing fibrous cap thicknesses ( β= -0.905, p Conclusions: Thin-capped plaques with large atheromas, known predictors of plaque vulnerability, were shown to exhibit the greatest mechanical stress levels.

Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice

Considerable evidence indicates that type 1 T helper （Th 1）- and Th 17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） have a protective effect. However, the functions of diverse CD4＋ lymphocyte subsets in plaque rupture remain poorly understood because of a shortage of satisfactory plaque rupture models. Here, we established a murine model of atherosclerotic plaque rupture using a high-fat diet and collar placement on the carotid artery, and triggered plaque rupture by short-term stimulation with a combination of lipopolysaccharide, phenylephrine injection and cold in apolipoprotein E-knockout （ApoE-/-） mice. We investigated the associations between Thl cells, Th17 cells and Tregs and plaque rupture by PCR, flow cytometry, ELISA and immunohistochemistry. In total, 75% （18/24） of vulnerable plaques, but no stable plaques, showed rupture characteristics. The proportion of Th17 cells was increased among splenocytes after treatment, but the changes in the levels of Thl ceils and Tregs were not related to rupture. Furthermore, the treatment resulted in high levels of interleukin- 17 （IL-17） in the serum and in the region of plaque rupture, in vitro, IL-17 increased the level of apoptosis, a major factor associated with plaque rupture, in cultured murine vascular smooth muscle cells. Th17 cells and IL-17 may be involved in the disruption of vulnerable plaques triggered by short-term stimulation with lipopolysaccharide, phenylephrine injection and cold in ApoE-/-mice.