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Injury-induced enzymatic methylation of aging collagen in the extracellular matrix of blood vessels.

As a result of blood vessel injury, protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT), a normally intracellular enzyme, becomes trapped within the meshwork of the vascular extracellular matrix where it can methylate substrate proteins. In this investigation we examined the distribution of such altered aspartyl-containing substrate proteins in the vascular wall. Nearly 90% of all the altered aspartyl residues were inaccessible to intracellular PIMT. Proteins of the extracellular matrix were found to be the major repository of altered aspartyl-containing polypeptides in the blood vessel wall, accounting for approximately 70% of the total amount. Proteolytic cleavage of extracellular matrix proteins with cyanogen bromide (CNBr) revealed that collagens account for most of the altered aspartyl-containing proteins of the ECM. As a consequence of blood vessel injury, both type I and type III collagen along with other proteins were found to become methylated by injury-released PIMT. It is estimated that 1 cm of vein contains on the order of 5 x 10(14) altered aspartyl residues involving between 1% and 5% of the total extracellular protein.

Animals↗

Effects of collateral blood vessel ligation and electrical conditioning on blood flow in dog latissimus dorsi muscle.

Utilization of skeletal muscle as a myocardial substitute requires it to undergo two major modifications: mobilization to the site of action and adaptation to continuous activity. We have examined the effects of collateral blood vessel ligation, which would accompany mobilization, on blood flow in control and electrically conditioned canine latissimus dorsi (LD) muscle. Blood flows were measured at rest and during a vigorous isometric fatigue test. In 22 control muscles, electrical stimulation during the fatigue test resulted in a sevenfold increase in muscle blood flow (0.26 +/- 0.18 ml/g/min at rest, 1.69 +/- 0.84 ml/g/min during stimulation). No difference was detected in flow to distal and proximal portions of the muscle. In three muscles where collateral vessels were ligated immediately before measurement of blood flow, flow in the proximal portion of the muscle was not significantly different from control, but in the distal portion, stimulation failed to elicit an increase in flow (0.12 +/- 0.13 ml/g/min at rest, 0.16 +/- 0.07 ml/g/min during stimulation). In animals allowed a 3-week recovery period following collateral vessel ligation, stimulation-induced increases in blood flow were detected but remained lower than control. Muscles which had been conditioned by continuous electrical stimulation for 6-7 weeks at 2 or 10 Hz generated less peak isometric tension than controls (peak tension = 4.5 +/- 1.7 kg control, 2.4 +/- 0.7 kg following 2 Hz conditioning, 1.6 +/- 0.4 kg following 10 Hz conditioning). However, these muscles demonstrated an increased resistance to fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Origins and assembly of avian embryonic blood vessels.

Two processes by which embryonic blood vessels develop are well-known: angiogenesis (growth by budding and branching of existing vessels) and local formation of endothelial vesicles that coalesce with elongating vessels. The former process appears to be more prevalent, with the latter restricted to vessels that form near the endoderm-mesoderm interface. The contributions of endothelial cells formed by each of these processes to specific blood vessels has not been defined, however, nor have the origins of precursors (angioblasts) of intraembryonic endothelial populations been established. To identify the origins of endothelial cells, precursor populations from quail embryos were transplanted into chick embryos. Antibodies that recognize quail endothelial cells were applied to sections from chimeric embryos fixed 2-5 days after surgery. These experiments reveal that all intraembryonic mesodermal tissues, except the notochord and prechordal plate, contain angiogenic precursors. Many angioblasts emigrate from the grafted tissue, invading surrounding mesenchyme and contributing to the formation of arteries, veins, and capillaries in a wide area. The invasive behavior of these angioblasts is unlike that of any other embryonic mesenchymal cell type and represents a third process operating during embryonic blood vessel formation. Transplanted angioblasts, even those excised from quail trunk regions, form normal craniofacial vascular channels, including the cardiac outflow tract. These results demonstrate that the control over blood vessel assembly resides within the connective tissue-forming mesenchyme of the embryo, not within endothelial precursors.

Animals↗

The role of the carotid body chemoreceptors and carotid sinus baroreceptors in the control of cerebral blood vessels.

1. Cerebral blood flow was measured in 17 baboons, anaesthetized with pentobarbitone, paralysed with gallamine and mechanically ventilated and in which the right sinus and both aortic nerves had been cut and the left carotid sinus vascularly isolated. Later in each experiment, the head was artificially perfused with femoral arterial blood via the innominate artery.2. Stimulation of the carotid body chemoreceptors with venous blood invariably caused a rise in regional cerebral blood flow whether the head was naturally or artificially perfused. This response was almost completely abolished if the VIIth cranial nerves were cut intracranially.3. Regional cerebral blood flow varied inversely with carotid sinus pressure.4. After the remaining (left) sinus nerve had been cut, the cerebral vascular response to hypoxia was negligible and the response to hypercapnia was markedly reduced. Blood flow then varied with perfusion pressure.5. These results provide further evidence that cerebral blood vessels are reflexly controlled and that the peripheral arterial receptors are involved. Their action is most conspicuous in the vascular response to hypoxia and together with intrinsic factors in the cerebral vascular bed, they determine the size of the vascular response to changes in CO(2) and pressure.

Animals↗

Formation of new bone during vertical distraction osteogenesis of the human mandible is related to the presence of blood vessels.

We examined the effect of distraction rate on blood vessel growth in intramembraneous ossification after vertical distraction osteogenesis in the human mandible. Six edentulous patients (aged 60+/-9 years) with a severely atrophic mandible underwent bone augmentation with distraction osteogenesis. Two distraction rates (0.5 and 1 mm/day) were compared and for each group three patients were analyzed. Vascular histomorphometry was carried out in two different areas in the distraction gap: (1) in the first and (2) in the second 1 mm area from the osteotomy line, representing the oldest and younger new-bone area, respectively. Correlation analysis was performed between blood vessel parameters and the amount of new bone formed during distraction. Histological analysis demonstrated the presence of blood vessels throughout the soft connective tissue in the distraction gap. The volume density of blood vessels between the two investigated areas was significantly lower in the 1 mm/day groups, suggesting a delay in angiogenesis in this group of patients. A positive correlation between blood vessel volume and bone volume density was found in the younger new-bone area but not in the oldest new-bone area. This correlation was due to a higher number of blood vessels rather than to a larger size of the blood vessels. Our data suggest that the lower blood vessel density found in the patients with 1 mm/day distraction rate may be related to disruption of angiogenesis in the soft connective tissue of the gap or to a less optimal mechanical stimulation of cells involved in angiogenesis. This probably results in the slower rate of osteogenesis seen at the 1 mm/day distraction rate compared with the 0.5 mm/day distraction rate. The data support the concept that a positive relationship exists between the density of blood vessels and the formation of bone. For distraction of the human mandible in elderly patients, a distraction rate of 0.5 mm/day seems beneficial.

Age Factors↗

Unusual blood vessels in the cochlea of the squirrel monkey.

Unusual blood vessels in the cochlea of the squirrel monkey are reported. The blood vessels in Reissner's membrane and basilar membrane are occasionally found in the course of the experimental middle ear study. The blood vessel of Reissner's membrane derives from a radiating arteriole in the upper spiral ligament and takes a straight course down to the inner surface of the spiral limbus, running on the scala vestibuli side of Reissner's membrane, and finally joins the venous vessel of the spiral limbus. Two blood vessels are noted in the basilar membrane of basal turn, running fairly parallel to each other from the tympanic lip to the basilar crest of the spiral ligament in the same cochlea. It is confirmed that these unusual blood vessels derive from the radiating arterioles in the osseous spiral lamina and connect with the venules of the basilar crest in the spiral ligament. Although unusual blood vessels in both Reissner's membrane and basilar membrane are thought to be vestigial structures, they contain a remarkable amount of alkaline phosphatase in their walls. This suggests that these unusual vessels have actually functioned until their death. Multiple occurrence of unusual blood vessels in both Reissner's membrane and basilar membrane of the cochlea of various animals, including man, has not yet been reported in the literature as far as we have been able to ascertain. Incomplete devascularization in the developing process of the cochlea may possibly be the cause of such unusual conditions after birth.

Animals↗

The role of pericytes in blood-vessel formation and maintenance.

Blood vessels are composed of two interacting cell types. Endothelial cells form the inner lining of the vessel wall, and perivascular cells--referred to as pericytes, vascular smooth muscle cells or mural cells--envelop the surface of the vascular tube. Over the last decades, studies of blood vessels have concentrated mainly on the endothelial cell component, especially when the first angiogenic factors were discovered, while the interest in pericytes has lagged behind. Pericytes are, however, functionally significant; when vessels lose pericytes, they become hemorrhagic and hyperdilated, which leads to conditions such as edema, diabetic retinopathy, and even embryonic lethality. Recently, pericytes have gained new attention as functional and critical contributors to tumor angiogenesis and therefore as potential new targets for antiangiogenic therapies. Pericytes are complex. Their ontogeny is not completely understood, and they perform various functions throughout the body. This review article describes the current knowledge about the nature of pericytes and their functions during vessel growth, vessel maintenance, and pathological angiogenesis.

Animals↗

[Pulmonary blood vessels in goats].

The blood vessels in the lung of the goat, which until now have received little attention, are described in detail for the first time. With regard to the segments of the lung, blood vessels are bronchovascular units in the lobi craniales, lobus medius and lobus accessorius, but bronchoartery units in the lobi caudales. We investigated the types of branches of the Aa. pulmonales dextra et sinistra, the inter- and intraspecific principles of the outlet of the pulmonary veins and the importance of bronchopulmonary segmentation of the lungs.

Animals↗

The ultrastructure of age-associated intimal fibrosis in pulmonary blood vessels.

The pulmonary blood vessels were examined from five human lungs surgically resected for bronchial carcinoma. Age-associated intimal fibrosis in these vessels was acellular in veins but more cellular in muscular pulmonary arteries. In both classes of vessel the cell involved in the production of this fibrosis was the myofibroblast, a cell which shares the properties of fibroblast and smooth muscle. The endothelial cells of pulmonary arteries contained numerous, uniform filaments with a random orientation but such filaments were rare in veins.

Aged↗

Blood vessel constitutive models-1995-2002.

Knowledge of blood vessel mechanical properties is fundamental to the understanding of vascular function in health and disease. Analytic results can help physicians in the clinic, both in designing and in choosing appropriate therapies. Understanding the mechanical response of blood vessels to physiologic loads is necessary before ideal therapeutic solutions can be realized. For this reason, blood vessel constitutive models are needed. This article provides a critical review of recent blood vessel constitutive models, starting with a brief overview of the structure and function of arteries and veins, followed by a discussion of experimental techniques used in the characterization of material properties. Current models are classified by type, including pseudoelastic, randomly elastic, poroelastic, and viscoelastic. Comparisons are presented between the various models and existing experimental data. Applications of blood vessel constitutive models are also briefly presented, followed by the identification of future directions in research.

Animals↗

Sympathetic co-activation of skin blood vessels and sweat glands.

Skin blood vessels and sweat glands are both innervated by sympathetic C fibers. We investigated whether during diverse respiratory maneuvers the vasomotor responses (VRs) and the sympathetic skin responses (SSRs) were frequently or occasionally co-activated. We simultaneously recorded the amplitude of the vasomotor responses and the sympathetic skin responses, the ECG and the respiratory movements in 30 healthy subjects during natural breathing at rest, rhythmic respirations at 6 per minute, sudden deep inspiration and Valsalva maneuver. We found: 1) The SSR habituates with all respiratory maneuvers whereas the VRs do not habituate. 2) There was slight co-activation between the SSRs and VRs during natural default breathing (56 percent). 3) During rhythmic breathing at 6 per minute the VRs and the SSRs were frequently co-activated (97 percent). The SSR appeared at the end of the inspiration coinciding with the end of the decreased blood flow. However the SSR habituated after few rhythmic respirations. 4) During sudden deep inspiration one hundred percent of co-activations were between the initial phase of the VRs and the SSR. The SSR is large in amplitude and longer in duration than during rhythmic breathing. 5) During the Valsalva maneuver there was a strong co-activation (100 percent) particularly during the phases II and III that are characterized by vaso-constriction but also during phase IV. The SSR is the longest of duration in all of the maneuvers. The sympathetic innervation to the sweat glands of the palm of the hand and to the skin blood vessels of the fingertips is differentiated. Under normothermic conditions sudden deep inspiration and Valsalva maneuver induced a large sympathetic simultaneous outflow to the skin blood vessels and sweat glands. The simultaneous recording of skin blood flow and the SSRs provides a more complete assessment of the sympathetic outflow to the skin than either one alone.

Adolescent↗

Closed contour edge detection of blood vessel lumen and outer wall boundaries in black-blood MR images.

Quantitative measurements of the blood vessel wall area may provide useful information of atherosclerotic plaque burden, progression and/or regression. Magnetic resonance imaging is a promising technique for identifying both luminal and outer wall boundaries of the human blood vessels. Currently these boundaries are primarily defined manually, a process viewed as labor intensive and subject to significant operator bias. Fully automated post-processing techniques used for identifying the lumen and wall boundaries, on the other hand, are also problematic due to the complexity of signal features in the vicinity of the blood vessels. The goals of this study were to develop a robust, automated closed contour edge detection algorithm, apply this algorithm to high resolution human carotid artery images, and assess its accuracy, and reproducibility. Our algorithm has proven to be sensitive to various contrast situations and is reasonably accurate and highly reproducible.

Algorithms↗

What are the residual stresses doing in our blood vessels?

We show that the residual strain and stress in the blood vessels are not zero, and that the zero-stress state of a blood vessel consists of open-sector segments whose opening angles vary along the longitudinal axis of the vessel. When the homeostatic state of the blood vessel is changed, e.g., by a sudden hypertension, the opening angle will change. The time constant of the opening angle change is a few hours (e.g., in the pulmonary artery) or a few days (e.g., in the aorta). From a kinematic point of view, a change of opening angle is a bending of the blood vessel wall, which is caused by a nonuniformly distributed residual strain. From a mechanics point of view, changes of blood pressure and residual strain cause change of stress in the blood vessel wall. Correlating the stress with the change of residual strain yields a fundamental biological law relating the rate of growth or resorption of tissue with the stress in the tissue. Thus, residual stresses are related to the remodeling of the blood vessel wall. Our blood vessel remodels itself when stress changes. The stress-growth law provides a biomechanical foundation for tissue engineering.

Animals↗

Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells.

Compared to native blood vessels, all clinically available blood vessel substitutes perform suboptimally. Numerous approaches to tissue engineer (TE) blood vessels have been pursued using different scaffold materials, cell types, and culture conditions. Several limitations however remain to be overcome prior to the potential application in the arterial system. This study aimed at tissue engineering viable ovine blood vessels suitable for implantation into the systemic circulation of sheep. In recent studies vascular smooth muscle cells (vSMC) were derived by an explant technique. However, in this study we show that homogenous populations of differentiated vSMC were only obtained by enzymatic dispersion as characterized by immunostaining for specific vSMC marker proteins. In contrast the explant method yielded predominantly less differentiated myofibroblast-like cells. Enzymatically derived vSMC were seeded onto P-4-HB scaffolds and incubated either in a pulsatile flow bioreactor or under static conditions. Dynamically cultured TE blood vessel substitutes showed confluent layered tissue formation and were completely water resistant. They displayed significantly increased ECM synthesis, DNA, and protein content as well as vSMC marker expression. Mechanical properties of bioreactor cultured TE blood vessels approached those of native aorta. In conclusion ovine, aortic blood vessel substitutes were successfully created using enzymatically derived vSMC, bioabsorbable scaffolds, and applied shear stress.

Animals↗

Toward a new blood vessel.

Strategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting (CABG), in which grafts are used to bypass atherosclerotic vessels and restore blood flow to the ischemic myocardium. The grafts used include healthy arteries or veins harvested from a separate site. Results with arterial grafts have been superior to venous grafts; promoting the practice of total arterial revascularization using only arterial grafts. Suitable arterial grafts, however, are scarce and harvest procedures add to morbidity and cost. Tissue engineering combines the principles of engineering with life sciences for the development of biological substitutes and restore, maintain or improve tissue function. Advances in this field have included the development of tissue-engineered blood vessels, with the potential to serve as arterial grafts, conduits or fistulae. This review describes the history of tissue engineering arteries, the techniques used, and progress to date. The source of cells and the future direction of this field are explored.

Blood Vessel Prosthesis↗

Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography.

Optical tissue clearing by hyperosmotic chemical agents significantly increases light depth penetration in skin and may improve light-based therapeutics such as laser treatment of cutaneous vascular lesions. A feasibility study was conducted to evaluate the potential role of optical clearing by glycerol in laser treatment of cutaneous vessels. Optical imaging was performed to investigate the morphological effects of glycerol on blood vessels of skin. Blood vessels were imaged using Doppler optical coherence tomography in in vivo hamster skin treated with glycerol. Images were obtained from the subdermal side to assess morphological changes in the blood vessels caused by glycerol and from the epidermal side to assess enhanced Doppler imaging of blood vessels. Application of glycerol to the subdermis resulted in venule stasis and for prolonged treatment times, arteriole stasis. In cases where flow remained in arterioles, an improved Doppler signal was detected from blood vessels when imaging transepidermally compared with the native condition. Intensity images indicated changes in blood optical properties and improved contrast of skin cross sections after glycerol application. The observed optical and morphological effects were reversed upon hydration of the skin with phosphate-buffered saline. The combination of increased depth of light penetration and the temporary slowing or cessation of flow in blood vessels could mean improved laser treatment of vessels.

Animals↗