Carotid plaque inflammation is associated with cerebral microembolism in patients with recent transient ischemic attack or stroke: a pilot study.

Background: Cerebral infarcts distal to carotid stenoses are thought to be caused by emboli from inflamed, destabilized plaques. We hypothesized that microembolic signals (MES) on transcranial Doppler will be associated with carotid plaque inflammation on (18)F fluorodeoxyglucose positron-emission tomography (FDG PET) in recently symptomatic patients.

Methods And Results: Sixteen patients presenting with recent (47 ± 31 days) anterior circulation transient ischemic attack or minor stroke and 50% to 99% stenosis of the ipsilateral carotid bifurcation underwent FDG PET, high-resolution black-blood carotid MRI, and transcranial Doppler for detection of MES.

FDG-PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis.

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of (18)F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS).

Comparison of methods for magnetic resonance-guided [18-F]fluorodeoxyglucose positron emission tomography in human carotid arteries: reproducibility, partial volume correction, and correlation between methods.

Background And Purpose: Inflammation is a major risk factor for atherosclerotic plaque rupture and clinical events. Previous studies have shown that plaque [(18)F]fluorodeoxyglucose (FDG) uptake correlates with macrophage content. In this study we examined the reproducibility of 3 methods of quantifying plaque FDG uptake in the carotid arteries using positron emission tomography (PET).

Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity.

Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous late-onset disease involving skeletal muscle wasting and heart defects caused, in a minority of cases, by mutations in either of two genes encoding the inner nuclear membrane (INM) proteins, emerin and lamins A/C. Nesprin-1 and -2 are multi-isomeric, spectrin-repeat proteins that bind both emerin and lamins A/C and form a network in muscle linking the nucleoskeleton to the INM, the outer nuclear membrane, membraneous organelles, the sarcomere and the actin cytoskeleton. Thus, disruptions in nesprin/lamin/emerin interactions might play a role in the muscle-specific pathogenesis of EDMD.

Strategy for improved [(11)C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [(11)C]DAA1106.

Introduction: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [(11)C]DAA1106 ([(11)C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs.

Methods: A four-step synthetic route was devised to prepare DAA1123, the precursor for [(11)C]DAA1106.

Antagonism of platelet-derived growth factor by perivascular gene transfer attenuates adventitial cell migration after vascular injury: new tricks for old dogs?

Migration of adventitial fibroblasts contributes to vascular remodeling after angioplasty. This study has used perivascular gene transfer of a truncated platelet-derived growth factor PDGF receptor (PDGFXR) to investigate whether antagonism of PDGF signaling alters adventitial cell migration after balloon injury in rat carotid arteries. Adenoviruses coordinating expression of beta-galactosidase (LacZ) and PDGFXR or LacZ and green fluorescent protein (GFP) were applied to the perivascular surface of arteries and balloon injury performed 4 days later.

Imaging endothelin ET(B) receptors using [18F]-BQ3020: in vitro characterization and positron emission tomography (microPET).

The endothelin (ET) receptor system has been shown to play a role in a number of vascular diseases. We have synthesized 18F-and 11C-labeled radioligands to enable in vivo imaging of the fundamental processes involved in ET receptor pharmacology in normal and diseased tissue using positron emission tomography (PET). One aim is to elucidate the proposed role of the ET(B) subtype as clearing receptor, removing ET-1 from the circulation, and whether this is an important mechanism to limit the detrimental effects caused by upregulated ET-1 in disease.

Radionuclide imaging for the detection of inflammation in vulnerable plaques.

Imaging of atheromatous plaques has traditionally centered on assessing the degree of luminal stenosis. More recently it has become clear that the vulnerable atherosclerotic plaques responsible for the majority of life-threatening syndromes are characterized by high numbers of inflammatory cells and proteins. This has highlighted the urgent need for suitable imaging techniques that can identify and quantify levels of inflammation within atheromatous lesions.

Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging.

Background And Purpose: Carotid endarterectomy is currently guided by angiographic appearance on the assumption that the most stenotic lesion visible at angiography is likely to be the lesion from which future embolic events will arise. However, risk of plaque rupture, the most common cause of atherosclerosis-related thromboembolism, is dictated by the composition of the plaque, in particular the degree of inflammation. Angiography may, therefore, be an unreliable method of identifying vulnerable plaques.

Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification.

Vascular calcification predicts an increased risk for cardiovascular events/mortality in atherosclerosis, diabetes, and ESRD. Serum concentrations of alpha(2)-Heremens-Schmid glycoprotein, commonly referred to as fetuin-A, are reduced in ESRD, a condition associated with an elevated circulating calcium x phosphate product. Mice that lack fetuin-A exhibit extensive soft tissue calcification, which is accelerated on a mineral-rich diet, suggesting that fetuin-A acts to inhibit calcification systemically.

Imaging the vertebral artery.

Although conventional intraarterial digital subtraction angiography remains the gold standard method for imaging the vertebral artery, noninvasive modalities such as ultrasound, multislice computed tomographic angiography and magnetic resonance angiography are constantly improving and are playing an increasingly important role in diagnosing vertebral artery pathology in clinical practice. This paper reviews the current state of vertebral artery imaging from an evidence-based perspective. Normal anatomy, normal variants and a number of pathological entities such as vertebral atherosclerosis, arterial dissection, arteriovenous fistula, subclavian steal syndrome and vertebrobasilar dolichoectasia are discussed.

Nesprins: intracellular scaffolds that maintain cell architecture and coordinate cell function?

Nesprins are a recently discovered family of ubiquitously expressed intracellular proteins. Through alternative transcriptional initiation, termination and splicing, two genes - nesprin-1 and nesprin-2 (also known as syne-1 and syne-2) - give rise to many protein isoforms that vary markedly in size. The largest of these isoforms comprise a C-terminal transmembrane domain (the KLS domain) linked by a spectrin-repeat rod domain to an N-terminal paired, actin-binding, calponin-homology domain.

Smad7 gene transfer attenuates adventitial cell migration and vascular remodeling after balloon injury.

Objective: Migration of adventitial fibroblasts contributes to arterial remodeling after angioplasty. This study used vascular gene transfer of smad7 to investigate whether antagonism of transforming growth factor-beta1 signaling alters luminal loss and adventitial cell migration after balloon injury in rat carotid arteries.

Methods And Results: Adenoviruses coordinating expression of beta-galactosidase (beta-gal) and smad7 or beta-gal and green fluorescent protein (GFP) were applied to the perivascular surface of common carotid arteries.

Targeting the vulnerable plaque: the evolving role of nuclear imaging.

The majority of acute ischemic events relating to atherosclerosis are caused by plaque rupture and ensuing thrombosis. The risk of plaque rupture is dictated in part by plaque morphology, which in turn is influenced by pathophysiologic mechanisms at the cellular and molecular level. Anatomic imaging modalities such as intravascular ultrasound, high-resolution magnetic resonance imaging, and multislice computed tomography can identify morphologic features of the vulnerable plaque, such as a large lipid core and thin fibrous cap, but give little or no information regarding molecular and cellular mechanisms, such as endothelial function, macrophage activation, lipid transport and metabolism, and cell death.

Imaging of atherosclerosis -- can we predict plaque rupture?

Rupture of so-called vulnerable or unstable atherosclerotic lesions is responsible for a significant proportion of myocardial infarcts and strokes. However, timely identification of such plaques, in order to allow for aggressive local and systemic therapy, remains problematic. In order to address this problem, there is a need to develop techniques that can image the cellular, biochemical, and molecular components that typify the vulnerable plaque.