Role of hyperlipidemia in atherosclerotic plaque formation in the internal carotid artery

2006 ◽  
Vol 34 (6) ◽  
pp. 283-288 ◽  
Author(s):  
Levente Kerenyi ◽  
Laszlo Mihalka ◽  
Laszlo Csiba ◽  
Hajnalka Bacso ◽  
Daniel Bereczki
2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Collin G Johnson ◽  
Iulia M Graf ◽  
Stanislav Emelianov ◽  
Aaron B Baker

Little is know about the role of enzymatic regulation of glycosaminoglycans in the formation of atherosclerotic plaques. Heparanase is the only known mammalian enzyme that degrades the glycosaminoglycan heparan sulfate. We tested the hypothesis that heparanase could regulate atherogenesis and atherosclerotic plaque severity. We transduced human endothelial cells with lentiviruses expressing one of four different constructs expressing shRNA targeted to heparanase or a scrambled control sequence. These shRNA knocked down the expression of heparanase to 30-50% of wild type expression levels. These lines were selected using puromycin and confirmed for gene modulation using immunostaining and western blotting for heparanase. The ability to uptake lipids was tested using fluorescently labeled, oxidized low-density lipoprotein (OxLDL). We found that cells expressing 30% of the heparanase protein in wild type cells had increased uptake of OxLDL in comparison to wild type cells (1.8+0.1 versus 1.00+0.07 of normalized OxLDL uptake; p <0.05) . We also evaluated the formation of atherosclerosis in transgenic mice overexpressing the human heparanase gene (HPA-Tg). This mouse line was crossed with the ApoE knockout mouse line. We exposed mice from this HPA-Tg/ApoE KO line and from the ApoE KO line of 20 weeks of age to 6 weeks of a high fat diet. At week 2 we surgically implanted an extravascular cuff on the left carotid artery to create a region of disturbed flow and low shear stress. Following the surgery, we used a high resolution combined ultrasound and photoacoustic imaging system to image the flow and plaque morphology after 1 day, 2 weeks and 4 weeks post-implantation of the cuff. Overexpression of heparanase increases the formation and severity of atherosclerosis in this model. Color doppler imaging revealed the existence of oscillatory flow in the left common carotid artery due to the formation of atherosclerotic plaque. This analysis confirmed an increase in the inflammatory response and neointimal formation in response to the low endothelial shear stress induced by the cuff in the HPA models compared to the ApoE. Our studies support that heparanase is a powerful regulator of lipid uptake and atherosclerotic plaque formation in an animal model of hyperlipidemia.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Farid Khasiyev ◽  
Tatjana Rundek ◽  
Chensy Marquez ◽  
Clinton B. Wright ◽  
Ralph Sacco ◽  
...  

Background: Cervical internal carotid artery (ICA) tortuosity has been associated with vascular risk and stroke as well as genetic disorders related to abnormal extracellular matrix remodeling. It is plausible that dystrophic or aberrant arterial remodeling may therefore relate to cervical ICA tortuosity. We hypothesized that cervical ICA tortuosity relates to carotid dilatation, but not to traditional ultrasound (US) markers of atherosclerosis. Methods: Subjects of the NOMAS with available time-of-flight MRA were included in our study. Cervical ICA tortuosity was defined as a bend in the distal cervical ICA of > 90° as seen on MRA. We excluded subjects with < 5 cm of the cervical ICA visualized. Distensibility was calculated as the percentage excursion of the right CCA diastolic diameter during systole, which was assessed by high-resolution B-mode US of the right common carotid artery (CCA). We used multivariable logistic regression analyses to estimate odds ratios for the association of cervical ICA tortuosity and Doppler measures of carotid wall aging. Results: We visualized cervical ICA tortuosity in 468 NOMAS participants (mean age 64±8 years, 70% women, 70% Hispanic). It was present in 23% of subjects. In unadjusted models, cervical ICA tortuosity was more common in women (OR 2.34, 95% CI 1.34-4.11), Hispanics (OR 1.85, 95%CI 1.06-3.25) and those with higher diastolic blood pressures (OR per mm Hg 1.04, 95%CI 1.01-1.06), and less common among smokers (OR 0.23, 95%CI 0.07-0.78). In models adjusted for demographic and vascular risks, right CCA tortuosity was associated with ipsilateral larger CCA DD (OR 1.42, 95%CI 1.02-1.96) and borderline associated with lower distensibility (OR 0.94, 95%CI 0.87-1.01, P=0.06) but not with ipsilateral ICA IMT (OR 0.26, 95%CI 0.14-4.77), number of plaques (OR 1.08, 95%CI 0.76-1.53), maximum plaque thickness (OR 0.96, 95%CI 0.73-1.27), or plaque area (1.00, 95%CI 0.97-1.05). Conclusions: Cervical ICA tortuosity associates with ipsilateral cervical ICA dilatation and lower distensibility, but not with traditional US markers of atherosclerosis. The association with diastolic blood pressure suggests a role of steady, rather than pulsatile, hemodynamics in aberrant cervical ICA remodeling.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xianfeng Yan ◽  
Bin Xie ◽  
Guihai Wu ◽  
Jing Hu ◽  
Di Wang ◽  
...  

Interleukin-37 (IL-37) is unique in the IL-1 family since it broadly suppresses innate immunity and elevates in humans with inflammatory and autoimmune diseases. IL-37 shows definite groups and transcripts for human IL37 gene, but it is still not completely understood the effect and mechanisms of inflammatory response in endothelial cells. It is well accepted that endothelial dysfunction caused by inflammation is a key initiating event in atherosclerotic plaque formation, which leads to the occurrence and development of the cardiovascular adverse events in clinical since the inflammatory responses of endothelial cells could induce and enhance the deposition of extensive lipid and the formation of atherosclerotic plaque in the intima. Thus, it is essential to investigate the role and potential mechanisms in endothelial inflammatory response to prevent the formation and development of many cardiovascular diseases including atherosclerosis. So far, the recent studies have revealed that IL-37 is able to inhibit inflammatory response by suppressing the TLR2-NF-κB-ICAM-1 pathway intracellularly in human coronary artery endothelial cells (HCAECs). Further, the role of IL-37 may be related to the IL-18 pathway extracellularly and involved in the adhesion and transmigration of neutrophils in HCAECs.


Neurosurgery ◽  
2014 ◽  
Vol 74 (suppl_1) ◽  
pp. S83-S91 ◽  
Author(s):  
Robert E. Harbaugh ◽  
Akshal Patel

Abstract Carotid endarterectomy is a commonly performed operation to prevent stroke in patients who have asymptomatic or symptomatic internal carotid artery atherosclerotic stenosis. Carotid angioplasty and stenting has also been advocated for treatment of these patients. In this article, we address a number of questions for which a review of available data will advance our understanding of the role of carotid endarterectomy in stroke prevention. These include the following: Are carotid endarterectomy and carotid angioplasty and stenting equivalent procedures for the treatment of carotid artery disease? Which patients should be deemed at high risk for carotid endarterectomy? Should carotid endarterectomy be an urgent procedure in symptomatic patients with severe internal carotid artery stenosis? Finally, what is the role of carotid endarterectomy in asymptomatic patients? We also review the senior author's personal experience with &gt;2000 consecutive carotid endarterectomies, with special attention to his present approach to this operation. We believe that carotid endarterectomy, in experienced hands, is a minimally invasive operation that remains the procedure of choice for most patients with carotid artery disease who will benefit from invasive treatment.


1998 ◽  
Vol 11 (2) ◽  
pp. 199-201
Author(s):  
A. Blandino ◽  
M. Longo ◽  
F.M. Salpietro ◽  
C. Alafaci ◽  
C. Narbone ◽  
...  

We describe an unusual type of neurovascular conflict between an elongated internal carotid artery and the optic nerve-chiasma complex. The fundamental role of conventional MR and MR angiography in the demonstration of the neurovascular conflict is illustrated.


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