Walls Of Large Vessels Research Articles

Type-2 pericytes participate in normal and tumoral angiogenesis.

Tissue growth and function depend on vascularization, and vascular insufficiency or excess exacerbates many human diseases. Identification of the biological processes involved in angiogenesis will dictate strategies to modulate reduced or excessive vessel formation. We examine the essential role of pericytes. Their heterogeneous morphology, distribution, origins, and physiology have been described. Using double-transgenic Nestin-GFP/NG2-DsRed mice, we identified two pericyte subsets. We found that Nestin-GFP(-)/NG2-DsRed(+) (type-1) and Nestin-GFP(+)/NG2-DsRed(+) (type-2) pericytes attach to the walls of small and large blood vessels in vivo; in vitro, type-2, but not type-1, pericytes spark endothelial cells to form new vessels. Matrigel assay showed that only type-2 pericytes participate in normal angiogenesis. Moreover, when cancer cells were transplanted into Nestin-GFP/NG2-DsRed mice, type-1 pericytes did not penetrate the tumor, while type-2 pericytes were recruited during its angiogenesis. As inhibition of angiogenesis is a promising strategy in cancer therapy, type-2 pericytes may provide a cellular target susceptible to signaling and pharmacological manipulation in treating malignancy. This work also reports the potential of type-2 pericytes to improve blood perfusion in ischemic hindlimbs, indicating their potential for treating ischemic illnesses.

SAT0184 Pet/Ct Hybrid Imaging is Useful for Identification of Patients with Large Vessel Vasculitis

BackgroundIn the diagnosis of giant cell arteritis (GCA) with aortic involvement, fluorine-18-fluorodeoxyglucose positron emission tomography / computed tomography hybrid imaging ([18F]-FDG-PET/CT) has been demonstrated to be a powerful tool. Its...

Dual immunofluorescence study of citrullinated proteins in Alzheimer diseased frontal cortex

Deimination is a post-translational modification of proteins in which selected arginine amino acids are enzymatically converted to citrullines. Using dual-color immunofluorescence, the present study is the first to examine the frontal cortex of patients with Alzheimer's disease (AD) versus age-matched controls with an established monoclonal antibody (F95) against peptidyl-citrulline moieties. In AD specimens, a number of new findings were discovered, including evidence for deiminated proteins in extracellular plaques, the walls of large blood vessels, the nuclei of selective neurons immunoreactive for phosphorylated tau and numerous reactive astrocytes concentrated around extracellular plaques, ventricular surfaces and at the interface between the gray and white matter of the cortex. Although the identities of these citrullinated proteins remain largely unknown, the present study adds to the growing number of locations in which deiminated proteins may be found in the brains of patients with AD.

Halicephalobus gingivalisin and around equine vasculature

<i><scp>H</scp>alicephalobus gingivalis</i>in and around equine vasculature

Allergic myocardial infarction

Allergic myocardial infarction

APP mutations in the Aβ coding region are associated with abundant cerebral deposition of Aβ38

Aβ is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into oligomers, protofibrils and fibrils is considered a seminal event in the pathogenesis of AD. Aβ with C-terminus at residue 42 is the most abundant species in parenchymal deposits, whereas Aβ with C-terminus at residue 40 predominates in the amyloid of the walls of large vessels. Aβ peptides with other C-termini have not yet been thoroughly investigated. We analysed Aβ38 in the brains of patients with Aβ deposition linked to sporadic and familial AD, hereditary cerebral haemorrhage with amyloidosis, or Down syndrome. Immunohistochemistry, confocal microscopy, immunoelectron microscopy, immunoprecipitation and the electrophoresis separation of low molecular weight aggregates revealed that Aβ38 accumulates consistently in the brains of patients carrying APP mutations in the Aβ coding region, but was not detected in the patients with APP mutations outside the Aβ domain, in the patients with presenilin mutations or in subjects with Down syndrome. In the patients with sporadic AD, Aβ38 was absent in the senile plaques, but it was detected only in the vessel walls of a small subset of patients with severe cerebral amyloid angiopathy. Our results suggest that APP mutations in the Aβ coding region favour Aβ38 accumulation in the brain and that the molecular mechanisms of Aβ deposition in these patients may be different from those active in patients with familial AD associated with other genetic defects and sporadic AD.

68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors

BackgroundGa-[1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors.MethodsSixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed.ResultsThe mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation.ConclusionsIn this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.

The immunomorphological analysis of innervation of paraganglian chromaffin cells of mammalian arteries and heart

Innervation of chromaffin cells of paraganglia of the wall of mammalian large arterial vessels and heart (in rat, cat, and human) was studied by neuromorphological and immunohistochemical methods. There is established similarity in structure of specialized, “basket“-like nerve endings of the chromaffin cells (ChC) with pericellular nerve apparatuses of sympathetic and parasympathetic autonomic neurons. It is proposed to use immunohistochemical reaction for synaptophysin as method of selective detection of ChC of paraganglia and adrenal medulla. The conclusion is made that synaptophysin-positive terminals (SPPT) found on bodies of ChC and postganglionic neurons represent efferent, rather than afferent, synapses formed by myelinated axons of preganglionic fibers. It is suggested that ChC of paraganglia alongside with their characteristic endocrine function participate in complex mechanisms of chemoreceptor regulation of tissue homeostasis of mammalian blood vessels and heart.

Collective Cell Movements during Vasculogenesis

Group motility of endothelial cells is studied in vivo using a recently developed TIE1-YFP transgenic quail line and in cell cultures. Statistical analysis of motility data show that endothelial cell movements are guided by intercellular contacts, both during vasculogenic sprout formation and within the walls of large early vessels like the dorsal aortae and vitelline arteries. This coordinated, but unoriented cell motility turns into an organized migration towards the heart after the onset of circulation. To interpret our empirical findings, we propose a computational model of endothelial cell motility which includes a positive feedback between cell polarity and cytoskeletal expansion, as well as response to micromechanical cues from the environment.

The fate of Lernaeocera branchialis (L.) (Crustacea; Copepoda) in Atlantic cod, Gadus morhua L.

Lernaeocera branchialis, a copepod crustacean parasite of gadoids, represents a potential threat to both wild and farmed cod, Gadus morhua. The pathological changes associated with the early stages of experimental infection have previously been reported in detail, and this article describes the lesions associated with later chronic stages of experimental infection. Chronic infection is characterised by extravascular granuloma formation and proliferation of fibrovascular tissue around intact and fragmented, degenerate parasites within both the gill arch and cardiac region. The majority of parasite granulomas are located within connective tissues of the gill arch or pericardium; however, low numbers are present within the wall of large vessels. The intraluminal parasites and thrombi of early stage infection are largely absent in these later lesions. We propose that organisation and incorporation of the parasite thrombus into the vessel wall with subsequent granuloma formation and extrusion into the surrounding connective tissue leads to the elimination of the parasite from the vascular system. Thus, rather than being a negative consequence of infection thrombosis is protective, allowing the host to survive the substantial initial vascular insult.

Takayasu's Arteritis in a Patient with Crohn's Disease: An Unexpected Association during Infliximab Therapy

We report a 20-year-old woman with Crohn's disease (CD) who developed anterior neck pain while being treated with the anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab. She showed no symptoms suggestive of active CD except for tenderness along the left common carotid artery with marked increases in serum TNF-alpha and inflammatory reactions. Based on thickened walls of large vessels with enhancement effects on computed tomography, she was diagnosed as having associated Takayasu's arteritis (TA), which was successfully treated with corticosteroid. Even if CD is controlled by infliximab, other autoimmune disorders, such as TA, may develop as a complication.

PET-CT findings in large vessel vasculitis presenting as FUO, a case report

There are increasing data demonstrating the role of flourodeoxyglucose positron emission tomography with computerized tomography fusion ((18)FDG PET-CT) in the diagnosis of large vessel vasculitides, including Takayasu arteritis and giant cell arteritis (Hara et al. 1999; Blockmans et al. 1999; Turlakow et al. 2001]. We report a case of large vessel giant cell arteritis involving the major branches of the aorta as detected on (18)FDG PET-CT. A 56-year-old woman returning to the USA after visiting her native Iraq presented to our rheumatology department with fever of unknown origin (FUO) of 2-month duration, night sweats, and arthralgias. The patient did not have claudication; systolic blood pressure measurements demonstrated a 20-mmHg difference between her arms. Infectious disease, malignancy, and collagen vascular disease workup was unrevealing. Temporal artery and bone marrow biopsies were negative. To exclude FUO of malignancy, (18)FDG PET-CT imaging was performed. The images demonstrated significant (18)FDG uptake (indicating increased metabolic activity) in a circumferential fashion along the aorta and its major braches, including the carotid, subclavian, and common iliac arteries. Contrast-enhanced CT imaging demonstrated wall thickening involving these vessels along with left subclavian vein thrombosis and findings consistent with superficial thrombophlebitis involving the right forearm, wrist, and hand. The combination of laboratory and imaging findings, including the characteristic inflammatory changes involving the large vessel walls as seen on CT, as well as the vessel wall hypermetabolism on FDG PET indicating active inflammation, resulted in the diagnosis of large vessel giant cell arteritis. The patient was treated with high-dose corticosteroids followed by a course of Immuran. Her symptoms resolved and a follow-up FDG PET-CT showed complete resolution of the large vessel hypermetabolism. (18)F-FDG PET-CT can be a useful and noninvasive tool in diagnostic evaluation of FUO by excluding a malignant etiology and providing unexpected information that aids in correct diagnosis.

A Spectrum of Knock-Type Doppler Signals in the Intracranial Vessels

Knock-type Doppler signals (KTDS) are detectable by transcranial Doppler, and it has been hypothesized that they are related to an occlusion of a small perforating artery and microvascular ischemia. However, the nature of KTDS has not been prospectively defined. We aimed at describing the spectral and power motion Doppler characteristics of KTDS and ultrasound exposure conditions that lead to their appearance. Consecutive patients referred with symptoms of stroke or transient ischemic attacks to our cerebrovascular ultrasound laboratory were screened for the presence of KTDS. The presence of microvascular ischemia was assessed using brain MRI. Among 327 patients with cerebrovascular symptoms, 46 (14%) had KTDS. KTDS were found more frequently in posterior circulation vessels (55% vertebral artery, 21.5% basilar artery, and 6% posterior cerebral artery). There was no association between ultrasound identification of KTDS and the presence of brain ischemia in the distribution of any vessel (OR, 0.37; 95% CI, 0.09-1.53; P=0.171) on univariate logistic regression analyses. KTDS was not related to the presence of microvascular ischemia on brain MRI (OR, 1.12; 95% CI, 0.55-2.29; P=0.761). We described the range of spectral and power motion Doppler appearances of KTDS and experimentally demonstrated the most likely underlying mechanism being a large vessel wall movement artifact. Although KTDS can be distinguished from other spectral flow signals, they can be found in normal vessels, they do not seem to be associated with the vessel affected by ischemia, and they should not be overinterpreted.

Léiomyosarcome veineux mimant une thrombose veineuse profonde : intérêts de la tomographie par émission de positrons

Leiomyosarcomas are rare malignant mesenchymal tumors. We report the case of a 55-year-old man with a lung metastasis from an iliofemoral leiomyosarcoma mimicking a deep venous thrombosis (DVT). Vascular leiomyosarcoma occurs in the wall of large vessels, and usually presents as unexplained DVT. To date, few cases of peripheral leiomyosarcomas have been described in the literature. This observation demonstrates the usefulness of Positron Emission Tomography (PET), beyond oncologic staging, in such indications as the workup of an unexplained DVT. In this report, PET prevented a misdiagnosis of DVT by showing a peculiar cockade appearance of the vessel. Compared with conventional imaging, PET can provide complementary information. The specificity of such information still needs to be assessed.

A randomized, double-blind study of valsartan versus metoprolol on arterial distensibility and endothelial function in essential hypertension

Antihypertensive drugs may have differential, pressure-independent effects on hypertension-associated alterations of arterial function. We compared the effects of a 12-week therapy with the AT(1)-receptor antagonist valsartan (Val) versus the beta-blocker metoprolol (Met) on arterial stiffness and endothelial function in mildly hypertensive patients at rest and during generalized sympathetic stimulation. Sixty-eight patients (37 male, 31 female, 46 +/- 6 years) were randomized to Val (80-160 mg/d) or Met (50-100 mg/d). Effects of therapy on endothelial function, brachial and carotid artery distensibility coefficients, pulse wave velocity, carotid intima-media thickness and elastic modulus were assessed at rest and during the cold pressor test. Fifty-two patients were available for per protocol analysis. Blood pressure was comparably reduced in both treatment groups. Effects on endothelial function and large artery elastic wall properties did not differ significantly between the two antihypertensive treatment regimens. Trends did not differ significantly between groups for any parameter including carotid intima-media thickness and elastic modulus. Short-term treatment with Val and Met had similar effects on large artery functional vessel wall properties in a population of mildly hypertensive patients.

Lycat and cloche at the Switch Between Blood Vessel Growth and Differentiation?

See related article, pages 1057–1064 The formation of the cardiovascular system starts in the mouse embryo at approximately embryonic day (E)7.0 to E7.5. The first blood vessels in the extraembryonic membranes, the major intraembryonic vessels, and the heart form by vasculogenesis, the in situ differentiation of mesodermal cells that give rise to “blood-islands.” The latter are composed of hemangioblasts, the common precursors of endothelial and blood cells. Hemangioblasts situated in the lumen of the blood islands will further differentiate into hematocytoblasts, the precursors of all 3 lineages of blood cells. In contrast, hemangioblasts lining the walls of the blood islands will give rise to angioblasts that form endothelial cells.1 Migrating angioblasts from the proximal lateral mesoderm assemble symmetrically at the lateral sides of the embryo to establish 2 preendocardial tubes. They fuse to give rise to the primordial heart.2 While vasculogenesis is still proceeding, the uniform blood islands begin to remodel to a network of large and small vessels by the process of angiogenesis, preferentially intussusceptive microvascular growth.3,4 Gene expression and targeting studies have identified vascular endothelial growth factor and its 2 receptors, KDR/flk-1 and flt-1, as critical for the formation and early remodeling of the blood islands. Vascular endothelial growth factor is produced by endodermal and mesodermal cells at the onset of hemangioblast formation, whereas its receptors are expressed in the future endothelial cells lining the blood islands.5 Flk-1−/− embryos lack blood islands throughout the embryo and yolk sac.6 In flt-1−/− embryos, blood islands do not properly remodel but form large blood channels.7 Inactivation of a single vascular endothelial growth factor allele caused multiple embryonic malformations including the heart, rudimentary dorsal aortae, and a reduced number of blood cells.8,9 All deletions were lethal between days E8.5 and E11 to …

High-Frequency Subharmonic Pulsed-Wave Doppler and Color Flow Imaging of Microbubble Contrast Agents

A recent study has shown the feasibility of subharmonic (SH) flow imaging at a transmit frequency of 20 MHz. This paper builds on these results by examining the performance of SH flow imaging as a function of transmit pressure. Further, we also investigate the feasibility of SH pulsed-wave Doppler (PWD) imaging. In vitro flow experiments were performed with a 1-mm-diameter wall-less vessel cryogel phantom using the ultrasound contrast agent Definity™ and an imaging frequency of 20 MHz. The phantom results show that there is an identifiable pressure range where accurate flow velocity and power estimates can be made with SH imaging at 10 MHz (SH10), above which velocity estimates are biased by radiation force effects and unstable bubble behavior, and below which velocity and power estimates are degraded by poor SNR. In vivo validation of SH PWD was performed in an arteriole of a rabbit ear, and blood velocity estimates compared well with fundamental (F20) mode PWD. The ability to suppress tissue signals using SH signals may enable the use of higher frame rates and improve sensitivity to microvascular flow or slow velocities near large vessel walls by reducing or eliminating the need for clutter filters. ( E-mail: aneedles@visualsonics.com)

Engineering of an elastic large muscular vessel wall with pulsatile stimulation in bioreactor

Tissue engineering offers a new approach for the construction of vascular substitutes in vitro with proper mechanical properties. Although success has been made in the engineering of small blood vessels (<6 mm in diameter), it remains a challenge to engineer large vessels (>6 mm in diameter) due to their insufficient biomechanical property. In the current study, an elastic large vessel wall (6 mm in diameter) was engineered by loading a polyglycolic acid (PGA) unwoven fiber scaffold seeded with smooth muscle cells (SMCs) on a vessel reactor designed with dynamic culture conditions. SMCs were isolated from canine carotid artery and expanded before seeding on a PGA fiber mesh. The cell-seeded PGA mesh was then loaded on a vessel reactor and subjected to pulsatile stimuli. Grossly, an elastic vessel wall was formed after 8 weeks of dynamic engineering. Histological examination showed well-orientated smooth muscle cells and collagenous fibers in the group with dynamic culture. In addition, the phenotype of SMCs was confirmed by positive staining of smooth muscle α-actin and calponin. On the contrary, disorganized smooth muscle cells and collagenous fibers were observed in the group under static culture without stimuli. Furthermore, the engineered vessels under dynamic culture exhibited significant improvements on biomechanical property over the one from static culture. Our results indicate that the approach developed in the current work is efficient for large vessel engineering. This approach may also be suitable for the engineering of other tissues with muscular tubular structure.

TWO CASES OF TAKAYASU'S ARTERITIS AND TUBERCULOSIS

INTRODUCTION:Takayasu's arteritis (TA) is a chronic inflammatory disease that primarily affects the walls of large vessels. The presence of Langhan's giant cells and granulomas similar to those in tuberculous lesions in biopsy specimen described 60 years ago has implicated Mycobacterium tuberculosis in the pathogenesis of TA. It is reported that patients with TA have substantially higher tuberculin sensitivity or active tuberculosis (TB) than the general population. We present two cases that support this postulate.

Methodology to determine failure characteristics of planar soft tissues using a dynamic tensile test

Predicting the injury risk in automotive collisions requires accurate knowledge of human tissues, more particularly their mechanical properties under dynamic loadings. The present methodology aims to determine the failure characteristics of planar soft tissues such as skin, hollow organs and large vessel walls. This consists of a dynamic tensile test, which implies high-testing velocities close to those in automotive collisions. To proceed, I-shaped tissue samples are subjected to dynamic tensile tests using a customised tensile device based on the drop test principle. Data acquisition has especially been adapted to heterogeneous and soft biological tissues given that standard measurement systems (considered to be global) have been completed with a non-contact and full-field strain measurement (considered to be local). This local measurement technique, called the Image Correlation Method (ICM) provides an accurate strain analysis by revealing strain concentrations and avoids damaging the tissue. The methodology has first been applied to human forehead skin and can be further expanded to other planar soft tissues. The failure characteristics for the skin in terms of ultimate stress are 3 MPa±1.5 MPa. The ultimate global longitudinal strains are equal to 9.5%±1.9% (Green–Lagrange strain), which contrasts with the ultimate local longitudinal strain values of 24.0%±5.3% (Green–Lagrange strain). This difference is a consequence of the tissue heterogeneity, clearly illustrated by the heterogeneous distribution of the local strain field. All data will assist in developing the tissue constitutive law that will be implemented in finite element models.