scholarly journals Comparative lipid profiling of murine and human atherosclerotic plaques using high-resolution MALDI MSI

2021 ◽  
Author(s):  
Pegah Khamehgir-Silz ◽  
Stefanie Gerbig ◽  
Nadine Volk ◽  
Sabine Schulz ◽  
Bernhard Spengler ◽  
...  
Keyword(s):  
High Resolution ◽  
Maldi Mass Spectrometry ◽  
Atherosclerotic Plaques ◽  
Peripheral Arteries ◽  
Lipid Profiling ◽  
Multivariate Statistical ◽  
Atherosclerotic Lesions ◽  
Lipid Species ◽  
Marker Profile ◽  
Artery Disease

Abstract The distribution of atherosclerotic lesions in the aorta and its branches of ApoE knockout (ApoE−/−) mice is like that of patients with atherosclerosis. By using high-resolution MALDI mass spectrometry imaging (MSI), we aimed at characterizing universally applicable physiological biomarkers by comparing the murine lipid marker profile with that of human atherosclerotic arteries. Therefore, the aorta or carotid artery of male ApoE−/− mice at different ages, human arteries with documented atherosclerotic changes originated from amputated limbs, and corresponding controls were analysed. Obtained data were subjected to multivariate statistical analysis to identify potential biomarkers. Thirty-one m/z values corresponding to individual lipid species of cholesterol esters, lysophosphatidylcholines, lysophosphatidylethanolamines, and cholesterol derivatives were found to be specific in aortic atherosclerotic plaques of old ApoE−/− mice. The lipid composition at related vessel positions of young ApoE−/− mice was more comparable with wild-type mice. Twenty-six m/z values of the murine lipid markers were found in human atherosclerotic peripheral arteries but also control vessels and showed a more patient-dependent diverse distribution. Extensive data analysis without marker preselection based on mouse data revealed lysophosphatidylcholine and glucosylated cholesterol species, the latter not being detected in the murine atherosclerotic tissue, as specific potential novel human atherosclerotic vessel markers. Despite the heterogeneous lipid profile of atherosclerotic peripheral arteries derived from human patients, we identified lipids specifically colocalized to atherosclerotic human tissue and plaques in ApoE−/− mice. These data highlight species-dependent differences in lipid profiles between peripheral artery disease and aortic atherosclerosis.

scholarly journals Features of atherosclerotic lesions of the coronary and peripheral arteries among patients with various forms of ischemic heart disease

2019 ◽  
Vol 19 (2) ◽  
pp. 73-80
Author(s):  
Alexander R. Prudnikov
Keyword(s):  
Myocardial Infarction ◽  
Heart Disease ◽  
Coronary Arteries ◽  
Ultrasound Examination ◽  
Study Groups ◽  
Atherosclerotic Plaques ◽  
Syntax Score ◽  
Peripheral Arteries ◽  
Average Force ◽  
Atherosclerotic Lesions

The aim of the article. To determine the features of atherosclerotic lesions of the coronary and peripheral arteries in patients with various forms of coronary heart disease. Material and methods. Male patients with verified IHD diagnoses: stable angina pectoris of 2 FC and patients with myocardial infarction of different localization and severity were investigated. All of the examined patients were underwent ultrasound examination of peripheral arteries with assessment of vessel wall, intima-media complex and description of atherosclerotic plaques if they were presented in vessels. Results. The predominance of non-concentric atherosclerotic plaques of type 3 according to the classification of Gray-Weal and Geroulakos in peripheral arteries is noted. It was found that atherosclerotic plaques in the carotid arteries, combined with the thickening of the intima-media complex were more common in the group of patients with myocardial infarction. The amount of Syntax score I points, reflecting the severity of atherosclerotic lesions of the coronary arteries, did not differ significantly in the studied groups. The presence of direct correlation relationships of average force (p < 0,05) between the parameters of peripheral artery atherosclerosis severity and Syntax score I points, as well as the number of affected coronary arteries in the study groups was noted. Conclusion. The results indicate a close relationship between carotid and coronary atherosclerosis, which determines the importance of using ultrasound examination of peripheral arteries (in particular, brachiocephalic) to assess the risk of recurrent acute coronary events.

scholarly journals Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 735
Author(s):  
Greg Hutchings ◽  
Łukasz Kruszyna ◽  
Mariusz J. Nawrocki ◽  
Ewa Strauss ◽  
Rut Bryl ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Blood Vessel ◽  
Lower Extremity ◽  
Molecular Mechanisms ◽  
Lower Extremities ◽  
Tissue Response ◽  
Peripheral Arteries ◽  
Artery Disease ◽  
Lower Extremity Artery Disease

Currently, atherosclerosis, which affects the vascular bed of all vital organs and tissues, is considered as a leading cause of death. Most commonly, atherosclerosis involves coronary and peripheral arteries, which results in acute (e.g., myocardial infarction, lower extremities ischemia) or chronic (persistent ischemia leading to severe heart failure) consequences. All of them have a marked unfavorable impact on the quality of life and are associated with increased mortality and morbidity in human populations. Lower extremity artery disease (LEAD, also defined as peripheral artery disease, PAD) refers to atherosclerotic occlusive disease of the lower extremities, where partial or complete obstruction of peripheral arteries is observed. Decreased perfusion can result in ischemic pain, non-healing wounds, and ischemic ulcers, and significantly reduce the quality of life. However, the progressive atherosclerotic changes cause stimulation of tissue response processes, like vessel wall remodeling and neovascularization. These mechanisms of adapting the vascular network to pathological conditions seem to play a key role in reducing the impact of the changes limiting the flow of blood. Neovascularization as a response to ischemia induces sprouting and expansion of the endothelium to repair and grow the vessels of the circulatory system. Neovascularization consists of three different biological processes: vasculogenesis, angiogenesis, and arteriogenesis. Both molecular and environmental factors that may affect the process of development and growth of blood vessels were analyzed. Particular attention was paid to the changes taking place during LEAD. It is important to consider the molecular mechanisms underpinning vessel growth. These mechanisms will also be examined in the context of diseases commonly affecting blood vessel function, or those treatable in part by manipulation of angiogenesis. Furthermore, it may be possible to induce the process of blood vessel development and growth to treat peripheral vascular disease and wound healing. Reactive oxygen species (ROS) play an important role in regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. With regard to the repair processes taking place during diseases such as LEAD, prospective therapeutic methods have been described that could significantly improve the treatment of vessel diseases in the future. Summarizing, regenerative medicine holds the potential to transform the therapeutic methods in heart and vessel diseases treatment.

Das Komplementsystem

2012 ◽  
Vol 32 (04) ◽  
pp. 276-285 ◽  
Author(s):  
V. Frauenknecht ◽  
V. Schroeder
Keyword(s):  
Coronary Artery Disease ◽  
Complement System ◽  
Innate Immune System ◽  
Innate Immune ◽  
The Other ◽  
Atherosclerotic Plaques ◽  
Inflammatory Processes ◽  
Artery Disease ◽  
The Complement System ◽  
Novel Therapeutic

SummaryAtherosclerotic diseases such as coronary artery disease and ischaemic stroke are caused by chronic inflammation in arterial vessel walls. The complement system is part of the innate immune system. It is involved in many processes contributing to onset and development of atherosclerotic plaques up to the final stage of acute thrombotic events. This is due to its prominent role in inflammatory processes. In addition, there is increasing evidence that interactions between complement and coagulation provide a link between inflammation and thrombosis. On the other hand, the complement system also has an atheroprotective function through the clearance of apoptotic material.The knowledge of these complex mechanisms will become increasingly important, also for clinicians, since it may lead to novel therapeutic and diagnostic options. Therapies targeting the complement system have the potential to reduce tissue damage caused by acute ischaemic events. Whether early anti-inflammatory and anti-complement therapy may be able to prevent atherosclerosis, remains a hot topic for research.

Abstract 2771: Incidence of High Risk Atherosclerotic Lesions in Intracranial and Extracranial Carotid Arteries in Patients with Acute Ischemic Stroke: A 3.0T Magnetic Resonance Imaging Study

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Xihai Zhao ◽  
Huilin Zhao ◽  
Feiyu Li ◽  
Jie Sun ◽  
Ye Cao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Carotid Arteries ◽  
Atherosclerotic Plaques ◽  
Slice Thickness ◽  
Atherosclerotic Lesions ◽  
Vascular Beds

Introduction Rupture of vulnerable atherosclerotic plaques in the intracranial and extracranial carotid arteries could trigger ischemic stroke. However, the incidence of high risk atherosclerotic lesions in these vascular beds is not well known. This study sought to investigate the incidence of high risk atherosclerotic lesions in intracranial and extracranial carotid arteries in stroke patients using magnetic resonance (MR) imaging. Methods Seventy-five patients (mean age 62.7 years, 56 males) with acute ischemic stroke underwent MR imaging for index carotid arteries, assigned as the same side as the brain lesions, with a Philips 3.0T MR scanner. Intracranial carotid MR angiography was performed using 3D TOF sequence with FOV of 23 × 23 cm 2 , matrix of 256 × 256, and a slice thickness of 1mm. The multi-contrast vessel wall images (3D TOF, T1W, T2W, and MP-RAGE) were acquired for extracranial carotid arteries with FOV of 14 × 14 cm 2 , matrix of 256 × 256, and slice thickness of 2 mm. The intracranial artery includes middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA). The extracranial carotid artery was divided into internal carotid artery (ICA), bulb, and common carotid artery (CCA). Luminal stenosis for each intracranial and extracranial carotid segment was measured and graded (normal or mild = 0-29%, moderate =30-69%, severe=70-99%). Normalized wall index (NWI = wall area/total vessel area × 100%), and presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) and/or fibrous cap rupture in each extracranial carotid segment were determined. Results MCAs developed more severe stenotic lesions (24.6%), followed by extracranial carotids (16.5%), PCAs (5.4%), and ACAs (4.1%) in stroke patients ( Figure 1 A). For extracranial carotid arteries, ICAs showed the largest plaque burden as measured by NWI (44.3%±13.1%), followed by bulbs (39.4%±13%), and CCAs (37%±6.8%). Compared to CCAs, ICAs and bulb regions had more LRNCs (38.4% and 49.3% for ICA and bulb respectively) and IPH and/or rupture (11% and 9.6% for ICA and bulb respectively) ( Figure 1 B). Conclusions In patients with acute ischemic stroke, high risk atherosclerotic plaques can be found in both intracranial and extracranial carotid arteries, particularly in the MCA, ICA and bulb regions. Compared to extracranial carotid arteries, intracranial arteries develop more high risk lesions. The findings of this study suggest the necessity for early screening to detect high risk atherosclerotic lesions in these carotid vascular beds prior to cerebravascular events.

scholarly journals Mass Spectrometry Imaging Using Dynamically Harmonized FT-ICR at Million Resolving Power: Rationalizing and Optimizing Sample Preparation and Instrumental Parameters

2020 ◽  
Author(s):  
Mathieu Tiquet ◽  
Raphaël La Rocca ◽  
Daan van Kruining ◽  
Pilar Martinez-Martinez ◽  
Gauthier Eppe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Mass Spectrometry Imaging ◽  
Mass Range ◽  
Maldi Mass Spectrometry ◽  
Mass Accuracy ◽  
Ion Current ◽  
Resolving Power ◽  
Lipid Mass ◽  
The Stability

<p><i>MALDI mass spectrometry imaging (MSI) is a powerful analytical method giving access to the 2D localizations of compounds in a thin section of a sample. To properly discern isobaric compounds in complex biological samples, dynamically harmonized ICR cell (ParaCell©) has been introduce to achieve extreme spectral resolution. However, high resolution MS images realized on a 9.4T FTICR High resolution instrument with recommended parameters suffered from an abnormal shifting of m/z ratios pixel to pixel. Resulting datasets show poor mass accuracy measurements and resolutions under estimations. By following the behavior of the Total Ion Current in function of the number of laser shots, the abnormal mass shifting phenomenon has been linked to the stability of the Total Ion Current (TIC) during images acquisitions. An optimization of laser parameters is proposed in order to limit the observed mass shift to retain machine specifications during MSI analyses. It is also shown that the method has been successfully employed to realize quality MS images with resolution above 1,000,000 in the lipid mass range across the whole image.</i></p>

scholarly journals Hybrid technologies in surgical treatment of patients with concomitant atherosclerotic lesions of carotid and coronary arteries

2015 ◽  
Vol 17 (1) ◽  
pp. 45 ◽  
Author(s):  
A. M. Chernyavskiy ◽  
M. A. Chernyavskiy ◽  
T. Ye. Vinogradova ◽  
A. G. Yedemskiy
Keyword(s):  
Surgical Treatment ◽  
Coronary Arteries ◽  
Carotid Arteries ◽  
Rapid Development ◽  
Peripheral Arteries ◽  
Endovascular Techniques ◽  
Hybrid Procedures ◽  
Atherosclerotic Lesions ◽  
Hybrid Technologies ◽  
Revascularization Surgery

Cardiovascular diseases, which have their origins in atherosclerosis, are the "leaders" in morbidity and mortality among the population in many countries. Given the increase of elderly people in the population, it is important to choose the best strategy for surgical treatment of patients with combined atherosclerotic lesions of several arteries (coronary arteries, carotid arteries, peripheral arteries of the lower extremities, atherosclerosis visceral branches of the abdominal aorta). Currently, there is yet no common approach to the timing and sequence of revascularization surgery in this group of patients. The rapid development of endovascular techniques enables us to carry out the so-called hybrid procedures in patients with atherosclerotic lesions of several arteries. In this article we analyze different strategies that are used to manage patients with both coronary and carotid arteries atherosclerotic lesions.

High-resolution myocardial stress perfusion at 3 T in patients with suspected coronary artery disease

2007 ◽  
Vol 18 (2) ◽  
pp. 226-233 ◽  
Author(s):  
Carsten Meyer ◽  
Katharina Strach ◽  
Daniel Thomas ◽  
Harold Litt ◽  
Claas P. Nähle ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Resolution ◽  
Suspected Coronary Artery Disease ◽  
Stress Perfusion ◽  
Myocardial Stress ◽  
Artery Disease ◽  
Myocardial Stress Perfusion

Impact of Valve Surgery on Serum Osteopontin Levels in Patients with Mitral Regurgitation

Cardiology ◽  
2015 ◽  
Vol 130 (2) ◽  
pp. 82-86
Author(s):  
H.M. Gunes ◽  
G.B. Guler ◽  
E. Guler ◽  
G.G. Demir ◽  
S. Hatipoglu ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Left Ventricular ◽  
Valve Surgery ◽  
Lv Function ◽  
Vena Contracta ◽  
Atherosclerotic Lesions ◽  
Lv Dysfunction ◽  
Echocardiographic Parameters ◽  
Artery Disease ◽  
The Impact

Objective: Osteopontin (OPN), a sialoprotein present within atherosclerotic lesions, especially in calcified plaques, is linked to the progression of coronary artery disease and heart failure. We assessed the impact of valve surgery on serum OPN and left ventricular (LV) function in patients with mitral regurgitation (MR). Methods: Thirty-two patients with severe MR scheduled for surgery were included in the study. Echocardiography markers were assessed preoperatively and at 3 months following the surgery and matched with the serum OPN levels. Results: Valve surgery was associated with a reduction of the ejection fraction (EF) from 55.2 ± 6.3 to 48.8 ± 7.1% after surgery, p < 0.001. Following surgery, the OPN level was significantly higher than preoperatively (mean 245, range 36-2,284 ng/ml vs. 76, 6-486 ng/ml, p = 0.007). Preoperative OPN exhibited a slight negative correlation with the EF (r = -0.35, p = 0.04), and a moderate correlation with vena contracta (r = -0.38, p = 0.02). There were no other meaningful correlations between conventional echocardiographic parameters and OPN. Conclusion: Following valve surgery due to severe MR, patients exhibited a decrease in EF and an increase in OPN levels. The assessment of preoperative OPN failed to strongly predict probable LV dysfunction.

Abstract 511: Mrp8 And Mrp14,Endogenous Activators of Toll-lLke Receptor4, are Associated with Rupture-Prone Human Atherosclerotic Plaques

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mihaela G Ionita ◽  
Gerard Pasterkamp ◽  
Dominique deKleijn
Keyword(s):  
Atherosclerotic Plaque ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Inflammatory Status ◽  
Potential Marker ◽  
Plaque Phenotype ◽  
Histological Characteristics ◽  
Unstable Plaques ◽  
Human Carotid

Objectives : Atherosclerosis is a chronic, complex inflammatory process and is the underlying cause of stroke and myocardial infarction due to rupture of the atherosclerotic plaque leading to acute occlusion of the artery in the brain or heart. Macrophages, infiltrating atherosclerotic lesions, abundantly express Mrp8 and Mrp14. Recently Mrp8, Mrp14 and the complex Mrp8/14 have been identified as endogenous ligands of Tlr-4.The role of Tlr-4 in the development and progression of the atherosclerotic plaque is well recognized and it is associated with a rupture-prone plaque phenotype. Expression of Mrps in human plaques and its relation to plaque phenotype is unknown. For this, we investigated the levels of Mrp8, Mrp14 and Mrp8/14 complex in a large number of human atherosclerotic plaques. Methods and results : Mrp8, Mrp14 and Mrp8/14 were quantified by ELISAs in human carotid endarterectomy specimens (186 patients) and plaque phenotype was determined by immunohistochemistry. Mrp levels were higher in the unstable (58 fibro-atheromatous, 64 atheromatous) compared to the stable (64 fibrous) plaques: Mrp8 p = 0.001 ; Mrp14 p = 0.001 ; Mrp8/14 p = 0.01 . Concomitantly, Mrp8, Mrp14 and Mrp8/14 were associated with characteristics of unstable plaques: more macrophages ( p = 0.024; p = 0.002; p = 0.076 ), less smooth muscle cells ( p = 0.041; p = 0.001; p = 0.074 ), larger lipid core ( p = 0.001; p = 0.001; p=0.004 ), less collagen ( p = 0.440; p = 0.011; p = 0.372 ). Furthermore, Mrp plaque levels were positively correlated with the pro-inflammatory cytokines (IL-6 and IL-8) and matrix metalloproteinsases (MMP2, MMP8 and MMP9) plaque levels. EDA, marker of stable plaques, was negatively associated with Mrps plaque levels. Histological analysis revealed that Mrps are expressed by a subgroup of plaque macrophages localized in the plaque cap and shoulder, the most rupture-prone sites of an atherosclerotic plaque. Conclusions: We show that Mrp8, Mrp14 and Mrp8/14 are strongly associated with the histological characteristics and inflammatory status of human rupture-prone plaques and identify Mrps as a potential marker for rupture-prone plaques.

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