Abstract 3482: Increased Matrix Metalloproteinase-9 Expression is Correlated with Carotid Intraplaque hemorrhage in a Swine Model

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Zhong-Song Shi ◽  
Xiao-Bing Jiang ◽  
Jin-Shan Wang ◽  
Wei-Si Yuan ◽  
Dong-Hong Liu

Purpose: The limited number of large animal carotid atherosclerotic models restricts the preclinical evaluation of endovascular therapies. Carotid intraplaque hemorrhage may be associated with a higher risk of ischemic stroke in patients with carotid disease. In this study, we assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with vulnerable atherosclerotic carotid plaque and intraplaque hemorrhage in a Swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for MMP-9 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. Atherosclerotic changes were classified by AHA/Stary stage (type I to VI). The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of MMP-9 expression in the plaque with the vulnerable plaque and intraplaque hemorrhage was further analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 segments had vulnerable plaque (Stary IV to VI). Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal ( P <0.0001). Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for MMP-9 tended to be greater in the vulnerable plaque than in the stable plaque (8.69 ± 0.73% vs. 7.04 ± 0.94%, p=0.35). Areas positive for MMP-9 were significantly greater in the plaque with intraplaque hemorrhage than in the plaque without intraplaque hemorrhage (11.84 ± 1.22% vs. 6.63 ± 0.59%, p<0.001). On multivariate analysis, positive expression of MMP-9 was an independent predictor of intraplaque hemorrhage (p=0.007). Conclusion: Vulnerable carotid plaques with distal embolism were created in a Swine model of carotid atherosclerosis. Increased expression of MMP-9 may be associated with vulnerable carotid plaques, especially having the feature of intraplaque hemorrhage.

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kiyofumi Yamada ◽  
Masanori Kawasaki ◽  
Shinichi Yoshimura ◽  
Shigehiro Nakahara ◽  
Yoshikazu Sato

Background: Carotid artery stenosis is one of the major causes of ischemic stroke. Carotid intraplaque hemorrhage (IPH) plays a critical role in the progression of carotid atherosclerotic disease. Previous studies showed that IPH was associated with high intensity signal (HIS) on maximum intensity projection (MIP) images from routine three dimensional magnetic resonance imaging (3D-TOF MRA). The aim of this study was to evaluate the relationships among HIS, new ipsilateral ischemic stroke and a progression rate in carotid plaques with moderate stenosis. Materials and Methods: We included 45 carotid plaques with moderate stenosis (50% to 69%) in 45 patients who could be followed more than 12 months. Carotid IPH was defined as the presence of HIS in carotid plaque on MIP image from routine 3DTOF MRA using the criteria previously we published. We analyzed the relation between the presence of HIS in the plaques and new ischemic strokes and annual progression rate of carotid stenosis. Results: HIS in carotid plaque was present in 21 (47%) carotid arteries. Over a follow-up period of 24 ± 9 months, six ischemic strokes occurred ipsilateral to the index carotid artery. New ipsilateral ischemic stroke occurred more frequently in HIS positive group (6 of 21, 29%) than HIS negative group (0 of 24, 0%) (p=0.017). Annual progression rate of carotid stenosis is significantly higher in HIS positive group (+3.35%/year) than HIS negative group (-0.02%/year) (p= 0.0026). In multivariate regression analysis, HIS positive was an independent predictor for annual progression rate of carotid stenosis (p=0.003). Conclusions: HIS in carotid plaques on 3DTOF-MRA MIP images are associated with new ischemic stroke and higher annual progression rate of stenosis. Evaluation of HIS in asymptomatic moderate carotid stenosis can potentially provide risk stratification of new ipsilateral ischemic strokes.


Stroke ◽  
2021 ◽  
Author(s):  
Luca Saba ◽  
Valentina Nardi ◽  
Riccardo Cau ◽  
Ajay Gupta ◽  
Hooman Kamel ◽  
...  

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.


2021 ◽  
Author(s):  
Andjoli Davidhi ◽  
Vasileios Rafailidis ◽  
Evangelos Destanis ◽  
Panos Prassopoulos ◽  
Stefanos Foinitsis

Recent literature has shown that various carotid plaque features, other than stenosis, contribute to plaque vulnerability. Features such as surface morphology and plaque composition with distinct components (e.g. intraplaque hemorrhage, lipid core) have been associated with the increased risk of future cerebrovascular events. Ultrasonography constitutes the first line modality for the assessment of carotid disease and has traditionally been used to grade stenosis with high accuracy. Recenttechnological advances such as contrast-enhanced ultrasound and elastography increased the diagnostic yield of ultrasound in assessing the morphology of carotid plaques. The purpose of this review is to present the available literature on ultrasound elastography of the atherosclerotic carotid. Strain and shear wave elastography allow for the characterization of plaque components, thus indicating its nature and importantly, the plaque’s vulnerability. Shear wave elastography indices appear morerobust than Strain indices. Overall, elastography is a feasible method to distinguish vulnerable carotid plaques. There is, however, a need for larger and longer prospective controlled clinical studies in order to validate elastography as an imaging modality used for the detection of unstable carotid plaques.


2011 ◽  
Vol 19 (3) ◽  
pp. 314-321 ◽  
Author(s):  
Xiang Xie ◽  
Yi-Tong Ma ◽  
Yi-Ning Yang ◽  
Zhen-Yan Fu ◽  
Xiang Ma ◽  
...  

Aim: The relationship between alcohol consumption and carotid atherosclerosis has been reported in some epidemiological studies, but the results were conflicting. We investigated the association between alcohol intake and carotid atherosclerosis in the Han, Uygur, and Kazakh populations in Xinjiang in western China. Methods and results: The study population sample comprised 13,037 Chinese people (5277 Han, 4572 Uygur, and 3188 Kazakh) aged ≥35 years who participated in a cardiovascular risk survey between June 2007 and March 2010. Daily consumption of alcohol was determined by the number and frequency of alcoholic beverages consumed. Carotid-artery parameters, including common carotid artery intima–media thickness (CCA–IMT) and carotid plaques were measured using high-resolution B-mode ultrasonography. In the Han and Kazakh populations, CCA–IMT as a function of alcohol consumption was depicted as a J-shaped curve with a nadir for the alcohol-intake category of 20–29.9 g/day; In the Uygur population, a similar curve with a nadir of 30–49.9 g/day was observed. With respect to the prevalence of carotid plaques, we also observed similar curves in the Han and Kazakh populations, but not in the Uygur population. After adjustment for age, sex, blood pressure, body mass index, and smoking status, as well as levels of glucose, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol, the J-shaped curves remained. Conclusions: Our results indicated that alcohol consumption was associated with carotid atherosclerosis and that moderate drinking had an inverse association with carotid atherosclerosis. However, the definition of moderate drinking could be different in Han, Uygur, and Kazakh populations.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Senija Rašić ◽  
Damir Rebić ◽  
Sabaheta Hasić ◽  
Ismar Rašić ◽  
Marina Delić Šarac

Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (P<0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P<0.05) and plaque score on CA in these patients (P<0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS.


2012 ◽  
Vol 5 (5) ◽  
pp. 473-477 ◽  
Author(s):  
Xiao-Bing Jiang ◽  
Jin-Shan Wang ◽  
Dong-Hong Liu ◽  
Wei-Si Yuan ◽  
Zhong-Song Shi

2021 ◽  
Author(s):  
Yu Wang ◽  
Runhua Zhang ◽  
Yong Jiang ◽  
Miaoxin Yu ◽  
Huiyu Qiao ◽  
...  

Abstract BackgroundTo investigate the association between hemoglobin A1c (HbA1c) and intraplaque hemorrhage (IPH) in carotid atherosclerotic plaque detected by high-resolution magnetic resonance imaging (HR-MRI) in a community-based population. MethodsIn this cross-sectional, community-based study, a total of 598 participants were recruited from May 2015 to September 2019. All participants underwent carotid artery HR-MRI. Data on demographics, medical history, and physical examinations were obtained through face-to-face interview, and fasting blood sample were collected. HbA1c was determined using high-performance liquid chromatographic analysis. Presence or absence of carotid plaque IPH was determined by HR-MRI. Multiple stepwise logistic regression analysis was performed to investigate the association between HbA1c levels and carotid plaque IPH. ResultsOf the 598 participants, 317 (53.0%) had atherosclerotic plaques, and 25 (4.2%) had IPH in carotid arteries. HbA1c was associated with the presence of IPH (OR, 1.94; 95% CI, 1.38-2.73) in the univariate analysis, and the association remained significant after adjustment for age, sex, traditional vascular factors, high-sensitivity C-reactive protein, and other potential confounders (OR, 1.70; 95% CI, 1.14-2.52).ConclusionsThis study showed that high HbA1c was associated with carotid plaque IPH detected by HR-MRI, which suggests that individuals with high HbA1c may have a higher risk of developing vulnerable carotid plaques.


2000 ◽  
Vol 6 (1_suppl) ◽  
pp. 165-170 ◽  
Author(s):  
E. Kobayashi ◽  
J. Ono ◽  
S. Hirai ◽  
I. Yamakami ◽  
N. Saeki ◽  
...  

Distal embolism is a detrimental complication of stent placement for the carotid artery stenosis. To evaluate usefulness of B-mode ultrasonography (US) for the detection of unstable plaques in patients with carotid artery stenosis, we examined US in 46 arteries of 35 patients with carotid stenosis of >30%. The echogenicity of 46 carotid plaques was hyperechoic in 20 plaques, hypoechoic in 15, and mixed-echoic in 11. The echogenicity of carotid plaques was correlated with severity of carotid stenosis, ipsilateral stroke or T1A, heart attack, and risk factors of systemic atherosclerosis. Hypoechoic plaques were associated with severe carotid stenosis and ipsilateral ischemic event. Mixed-echoic plaques had a high incidence of past history of heart attack. Hyperechoic plaques were less likely to associate with risk factors of systemic atherosclerosis. We developed a new method of echodensity analysis. Using a computer software, echodensity values of seven plaque components were determined by comparing US findings and pathology of surgical specimens. The echodensity value was defined as a relative value to the arterial lumen. The calcified part of plaques had the highest echodensity of 6.24 ± 0.86 (mean ± 2 S.D.); fibrosis or hyarynoid degeneration of 2.05 ± 0.40, foamy histiocytes of 1.47 ± 0.05, necrosis of 1.32 ± 0.16, cholestelin clefts of 1.28 ± 0.13, intraplaque hemorrhage of 1.02 ± 0.09, and intraluminal thrombus of 1.27 ± 0.07. Constructed from the echodensity value, an echo-densitometry color mapping of the carotid plaque illustrated the exact location and extent of plaque component. B-mode US of carotid plaques represents clinical characteristics relating distal embolism and systemic atherosclerosis. A new method of echodensity analysis and echo-densitometry color mapping of the carotid plaque is useful to detect unstable plaques in patients with carotid stenosis.


2020 ◽  
Vol 182 (3) ◽  
pp. 343-350
Author(s):  
Blerim Mujaj ◽  
Daniel Bos ◽  
Maryam Kavousi ◽  
Aad van der Lugt ◽  
Jan A Staessen ◽  
...  

Background To investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque remains unclear. Methods In 1740 participants (mean age 72.9 years, 46% women, 14.4% diabetes mellitus) from the population-based Rotterdam Study, we performed carotid MRI to evaluate the presence of calcification, lipid core, and intraplaque hemorrhage in carotid atherosclerosis. All participants also underwent blood sampling to obtain information on serum insulin and glucose levels. Using logistic regression models, we assessed the association of serum insulin and glucose levels (per s.d. and in tertiles) with the different plaque components, while adjusting for sex, age, intima-media thickness, and cardiovascular risk factors. Results Serum insulin levels were associated with the presence of intraplaque hemorrhage (adjusted odds ratio (OR): 1.42 (95% CI: 1.12–1.7)) We found no association with the presence of calcification or lipid core. Sensitivity analyses restricted to individuals without diabetes mellitus yielded similar results. No associations were found between serum glucose levels and any of the plaque components. Conclusions Serum insulin levels are associated with the presence of vulnerable components of carotid plaque, specifically with intraplaque hemorrhage. These findings suggest a complex role for serum insulin in the pathophysiology of carotid atherosclerosis and in plaque vulnerability.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kenichi Sugioka ◽  
Takahiko Naruko ◽  
Takeshi Hozumi ◽  
Shoichi Ehara ◽  
Takuhiro Okuyama ◽  
...  

Background: Neopterin is produced by activated macrophages and serves as an activation marker for monocytes/macrophages. Serum levels of neopterin have been shown to be associated with the presence of complex coronary lesions in unstable angina pectoris. However, the relationship between neopterin levels and complex carotid lesions is still unknown. We investigated the association between plasma neopterin levels and the characteristics of carotid plaques in patients with stable angina pectoris (SAP). Moreover, we immunohistochemically studied the presence of neopterin in carotid endarterectomy specimens. Methods: We studied 65 SAP patients who were scheduled coronary angiography. In all patients, plasma neopterin levels were measured and carotid ultrasound was performed for evaluation of carotid artery plaque score (PS) defined by the sum of plaque thickness, plaque number (PN) and plaque surface irregularity. Frozen tissue of 40 endarterectomy specimens for extracranial high-grade carotid stenosis were immunohistochemically examed with antibodies against macrophages and neopterin. Results: There was no significant correlation between plasma neopterin levels and PS (P=0.38) or PN (P=0.49). On the other hand, plasma neopterin levels were significantly higher in patients with carotid plaque surface irregularity compared with patients without it (25.4 ± 13.5 nmol/L vs.16.9 ± 6.5 nmol/L, P=0.0015). Carotid plaque irregularity was detected more frequently in patients with higher neopterin levels (>=18.5 nmol/L median) compared with those with lower neopterin levels (41.9% vs. 16.1%, P=0.025). Using multivariate analyses, nepopterin levels (OR, 1.11; 95%CI, 1.01 to 1.21; P=0.023) and the number of diseased coronary vessels (OR, 2.51; 95%CI, 1.01 to 6.22; P=0.047) are independently associated with carotid plaque irregularity. Immunohistochemical staining showed abundant neopterin-positive macrophages in the unstable carotid plaques. Conclusions: Neopterin levels are associated with carotid complex plaques rather than the severity of carotid atherosclerotic change. Neopterin can be considered as one of the significant markers of plaque destabilization in not only coronary artery but carotid artery atherosclerotic lesions.


Sign in / Sign up

Export Citation Format

Share Document