Animal models of vulnerable plaque

2003 ◽  
Vol 90 (11) ◽  
pp. 774-780 ◽  
Author(s):  
Ik-Kyung Jang ◽  
Levon Khachigian ◽  
Harry Lowe

SummaryThere is increasing recognition of the importance of vulnerable plaque and acute plaque rupture leading to thrombosis, in the pathogenesis of acute coronary syndromes. This is fueling a number of developments, including novel imaging modalities and potential plaque stabilization therapies. However, to date, no animal model of vulnerable plaque or plaque rupture has been established. Recent developments, particularly using Apo E knockout mice, appear set to provide key breakthroughs. The present status of our understanding of plaque vulnerability is therefore discussed, with a discussion of these current advances in animal models.

Circulation ◽  
2002 ◽  
Vol 106 (7) ◽  
pp. 760-762 ◽  
Author(s):  
Paul Schoenhagen ◽  
E. Murat Tuzcu ◽  
Stephen G. Ellis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alexander Akhmedov ◽  
Keiko Yonekawa ◽  
Christophe Wyss ◽  
Roberto Corti ◽  
Nils Kucher ◽  
...  

Introduction: Monocytes and leucocytes (WBC) play a key role in acute coronary syndromes (ACS). We hypothesized that gene expression profiling of WBC from the site of coronary occlusion in direct comparison with peripheral WBC from patients with ACS might reveal genetic patterns involved in plaque rupture. Methods: Thrombi (Thr) were aspirated during primary percutaneous coronary intervention (PCI), snap-frozen, and stored at −80°C. Peripheral blood leukocytes (PBL) from the same patients were extracted and treated accordingly. Total RNA was isolated from thrombi and PBL. The quality and quantity of the isolated RNA was determined using bioanalyzer and nanodrop devices. The cDNA was prepared using a primer mix and reverse transcriptase, followed by fragmentation and biotinilation. Biotin-labeled single-stranded cDNA samples were hybridized to Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. An Affymetrix GeneChip Scanner was used to measure the fluorescent intensity emitted by the labelled target. Results: Gene expression profiles of Thr and PBL from 4 patients during PCI were assessed by Affymetrix human genome U133 Plus 2.0 arrays (54′675 probe sets). 653 different genes were locally upregulated in Thr compared to PBL as defined by a more than 8-fold difference in expression and statistical significance (p≤0.01). Genes for proteins of inflammation, thrombosis, endothelial activation, extracellular matrix remodelling, and scavenger receptors were highly upregulated at the site of coronary occlusion (examples see table 1 ). Conclusion: The local gene expression profile in WBC from thrombi differs significantly from the pattern in PBL, reflecting the regulatory and effective role of these cells in plaque rupture and thrombosis. This study identifies the upregulation of genes encoding for a host of established and new pathways involved in inflammation, uptake of oxidized LDL, and coagulation, that might play a crucial role in ACS. Table 1


2020 ◽  
Vol 21 (8) ◽  
pp. 2992
Author(s):  
Nataliya V. Mushenkova ◽  
Volha I. Summerhill ◽  
Dongwei Zhang ◽  
Elena B. Romanenko ◽  
Andrey V. Grechko ◽  
...  

Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed.


2011 ◽  
Vol 111 (2) ◽  
pp. 599-605 ◽  
Author(s):  
Arun Kumar ◽  
Subrata Kar ◽  
William P. Fay

Acute coronary syndromes (ACS) are common, life-threatening cardiac disorders that typically are triggered by rupture or erosion of an atherosclerotic plaque. Platelet deposition and activation of the blood coagulation cascade in response to plaque disruption lead to the formation of a platelet-fibrin thrombus, which can grow rapidly, obstruct coronary blood flow, and cause myocardial ischemia and/or infarction. Several clinical studies have examined the relationship between physical activity and ACS, and numerous preclinical and clinical studies have examined specific effects of sustained physical training and acute physical activity on atherosclerotic plaque rupture, platelet function, and formation and clearance of intravascular fibrin. This article reviews the available literature regarding the role of physical activity in determining the incidence of atherosclerotic plaque rupture and the pace and extent of thrombus formation after plaque rupture.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takashi Kubo ◽  
Yoshiki Matsuo ◽  
Yasushi Ino ◽  
Takashi Tanimoto ◽  
Kohei Ishibashi ◽  
...  

Background. Recent intravascular ultrasound (IVUS) studies have demonstrated that hypoechoic plaque with deep ultrasound attenuation despite absence of bright calcium is common in acute coronary syndrome. Such “attenuated plaque” may be an IVUS characteristic of unstable lesion.Methods. We used optical coherence tomography (OCT) in 104 patients with unstable angina to compare lesion characteristics between IVUS-detected attenuated plaque and nonattenuated plaque.Results. IVUS-detected attenuated plaque was observed in 41 (39%) patients. OCT-detected lipidic plaque (88% versus 49%, ), thin-cap fibroatheroma (48% versus 16%, ), plaque rupture (44% versus 11%, ), and intracoronary thrombus (54% versus 17%, ) were more often seen in IVUS-detected attenuated plaques compared with nonattenuated plaques.Conclusions. IVUS-detected attenuated plaque has many characteristics of unstable coronary lesion. The presence of attended plaque might be an important marker of lesion instability.


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