Study of normal and pathological blood vessel morphogenesis in Flt1-tdsRed BAC Tg mice

Blood vessel development and network patterning are controlled by several signaling molecules, including VEGF, FGF, TGF‐ß, and Ang‐1,2. Among these, the role of VEGF‐A signaling in vessel morphogenesis is best understood. The biological activity of VEGF‐A depends on its reaction with specific receptors Flt1 and Flk1. Roles of VEGF‐A signaling in endothelial cell proliferation, migration, survival, vascular permeability, and induction of tip cell filopodia have been reported. In this study, we have generated Flt1‐tdsRed BAC transgenic (Tg) mice to monitor Flt1 gene expression during vascular development. We show that tdsRed fluorescence is observed within blood vessels of adult mice and embryos, indicative of retinal angiogenesis and tumor angiogenesis. Flt1 expression recapitulated by Flt1‐tdsRed BAC Tg mice overlapped well with Flk1, while Flt1 was expressed more abundantly in endothelial cells of large blood vessels such as dorsal aorta and presumptive stalk cells in retina, providing a unique model to study blood vessel development. genesis 50:561–571, 2012. © 2012 Wiley Periodicals, Inc.     

Vascular anatomy of the lateral musculature of the flathead,Platycephalus bassensis (Teleostei: Perciformes)

Summary The vascular anatomy of the lateral musculature of the flatheadPlatycephalus bassensis, was studied by scanning electron microscopy of corrosion casts. Arteries and veins showed an alternating pattern in neighbouring vertebral segments. The red muscle was supplied by five major branches of the intermuscular artery, and the white muscle by infrequent branches of the intermuscular artery, dorsal segmental artery and ventral segmental artery. Venous drainage of the red and white muscles broadly mimicked the arterial supply. The functional unit of the trunk vasculature can be considered as an artery, a vein and connecting fine blood vessels. There appear to be 2 over-lapping types leading to alternating clockwise and counter-clockwise flows of blood. Small satellite vessels were observed running parallel to most of the larger blood vessels. No anatomical A-V shunt vessels, or series vascular connections between the red and white muscle, were observed. The irregular, alternating adult system is postulated to have developed from an earlier system showing strict bilateral symmetry and equal arterial and venous development in each vertebral segment.     

Blood vascular system of the sea cucumber,Stichopus moebii

Stichopus moebii, a sea cucumber, has a closed circulatory system which is unique in its degree of development for the phylum Echinodermata. The gross anatomy, histology and fine structure of the system were studied. Blood vessels consist of a coelomic surface of ciliated epithelium, a layer of muscle and nerve cells, followed by connective tissue and luminal lining of endothelium. Basically the blood vascular system consists of two major vessels running parallel to the gut: the dorsal vessel pumps colorless blood via the vessels within the walls of the intestine into the ventral vessel. There are two specialized areas of the circulation: (1) At the upper small intestine 120 to 150 muscular single-chambered hearts pump blood from the dorsal vessel into a series of intestinal plates. (2) At the lower region of the small intestine the vasculature is associated with the left respiratory tree. Blood passing from the dorsal pulmonary vessel can take two routes to the gut, it either passes through myriads of minute respiratory shunt vessels entangled with the respiratory tree or it passes through a unique follicle network consisting of tiny channels periodically dilated into chambers filled with iron deposits, necrotic cells and developing coelomocytes.     

The blood system of the flabelligerid polychaete Flabelliderma commensalis (Moore)

The blood system of the flabelligerid polychaete, Flabelliderma commensalis has been explored by dissection, light and electron microscopy and absorption spectrophotometry. The main longitudinal vessels are the dorsal, ventral, perineural, sub-oesophageal, supra-oesophageal and heart. Each segment has a segmental vessel which communicates with the dorsal vessel in thoracic setigers and the gut sinus in abdominal setigers. Branches of the segmental vessels in setigers 2–9 supply the gonads. A blood sinus envelopes most of the gut. Circulation is maintained by the pumping of the heart which immediately supplies blood to the supra-oesophageal ganglion, the branchiae and the palps. These are paralleled by a system of collecting vessels. The sinus of the supra-oesophageal ganglion receives a number of different axonal endings, some of which may be neurosecretory. The retroperitoneal vessels in their most developed form are composed of an intima, longitudinal and circular muscles and a peritoneum. The heart vessel contains a cardiac body whose cells appear to contain vacuoles of blood pigment. The blood pigment exhibits the absorption characteristics of a chlorocruorin with maxima at 438, 558 and 606 nm.     

The Fine Structure of Some Blood Vessels of the Earthworm, Eisenia foetida

The fine structure of the main dorsal and ventral circulatory trunks and of the subneural vessels and capillaries of the ventral nerve cord of the earthworm, Eisenia foetida, has been studied with the electron microscope. All of these vessels are lined internally by a continuous extracellular basement membrane varying in thickness (0.03 to 1 µ) with the vessel involved. The dorsal, ventral, and subneural vessels display inside this membrane scattered flattened macrophagic or leucocytic cells called amebocytes. These lie against the inner lining of the basement membrane, covering only a small fraction of its surface. They have long, attenuated branching cell processes. All of these vessels are lined with a continuous layer of unfenestrated endothelial cells displaying myofilaments and hence qualifying for the designation of "myoendothelial cells." The degree of muscular specialization varies over a spectrum, however, ranging from a delicate endowment of thin myofilaments in the capillary myoendothelial cells to highly specialized myoendothelial cells in the main pulsating dorsal blood trunk, which serves as the worm's "heart" or propulsive "aorta." The myoendothelial cells most specialized for contraction display well organized sarcoplasmic reticulum and myofibrils with thick and thin myofilaments resembling those of the earthworm body wall musculature. In the ventral circulatory trunk, circular and longitudinal myofilaments are found in each myoendothelial cell. In the dorsal trunk, the lining myoendothelial cells contain longitudinal myofilaments. Outside these cells are circular muscle cells. The lateral parts of the dorsal vessels have an additional outer longitudinal muscle layer. The blood plasma inside all of the vessels shows scattered particles representing the circulating earthworm blood pigment, erythrocruorin.     

Gill microcirculation of the air-breathing climbing perch, Anabas testudineus (Bloch):relationships with the accessory respiratory organs and systemic circulation

The general macrocirculation and branchial microcirculation of the air-breathing climbing perch, Anabas testudineus, was examined by light and scanning electron microscopy of vascular corrosion replicas. The ventral aorta arises from the heart as a short vessel that immediately bifurcates into a dorsal and a ventral branch. The ventral branch distributes blood to gill arches 1 and 2, the dorsal branch to arches 3 and 4. The vascular organization of arches 1 and 2 is similar to that described for aquatic breathing teleosts. The respiratory lamellae are well developed but lack a continuous inner marginal channel. The filaments contain an extensive nutritive and interlamellar network; the latter traverses the filament between, but in register with, the inner lamellar margins. Numerous small, tortuous vessels arise from the efferent filamental and branchial arteries and anastomose with each other to form the nutrient supply for the filament, adductor muscles, and arch supportive tissues. The efferent branchial arteries of arches 1 and 2 supply the accessory air-breathing organs. Arches 3 and 4 are modified to serve primarily as large-bore shunts between the dorsal branch of the ventral aorta and the dorsal aorta. In many filaments from arches 3 and 4, the respiratory lamellae are condensed and have only 1-3 large channels. In some instances in arch 4, shunt vessels arise from the afferent branchial artery and connect directly with the efferent filamental artery. The filamental nutrient and interlamellar systems are poorly developed or absent. The respiratory and systemic pathways in Anabas are arranged in parallel. Blood flows from the ventral branch of the ventral aorta, through gill arches 1 and 2, into the accessory respiratory organs, and then returns to the heart. Blood, after entering the dorsal branch of the ventral aorta, passes through gill arches 3 and 4 and proceeds to the systemic circulation. This arrangement optimizes oxygen delivery to the tissues and minimizes intravascular pressure in the branchial and air-breathing organs. The efficiency of this system is limited by the mixing of respiratory and systemic venous blood at the heart.     

Ultrastructural reinvestigation of the trophosome in adults of Riftia pachyptila (Annelida, Siboglinidae)

Abstract. The trophosome of adults of Riftia pachyptila (Vestimentifera) was reinvestigated using 3-dimensional ultrastructural reconstruction and quantitative morphological analysis. The symbionts make up 24.1%, the symbiont-containing cells (bacteriocytes) are 70.5% of the trophosome's volume. The trophosome is composed of lobules that have a central axial blood vessel surrounded by a myoepithelium containing bacteriocytes, in turn surrounded by an apolar tissue of bacteriocytes. Part of the splanchnic peritoneum lining the trunk coelom encases the bacteriocytes and forms a ramifying network of peripheral blood vessels. Based on the morphology and ultrastructure of the adult, we hypothesize a mesodermal rather than endodermal origin of trophosome and its constitute bacteriocytes. Some of the central bacteriocytes are part of the myoepithelium surrounding the axial blood vessel and act as stem cells for a proliferating tissue produced in the center and ultimately degraded at the periphery of each lobule. Similarly, the rod-shaped symbionts in the center act as stem cells and exhibit a simple cell cycle. Differentiation into cocci takes place in the median and peripheral zone. Lysis of cocci occurs in the degenerative zone.     

Haemodynamic effects of adenosine on gills of the trout (Salmo gairdneri)

Summary The haemodynamic effects of adenosine on gills of the trout (Salmo gairdneri) were studied with in vitro and in vivo preparations.On the isolated head preparation, adenosine induced a decrease of the ventral aortic inflow and of the dorsal aortic outflow. Simultaneously the venous outflow increased. These effects were antagonized by theophylline. Adenosine induced a vasoconstriction in gill arches without filaments perfused by the afferent or the efferent branchial arteries. The efferent vessels were more sensitive to adenosine than afferent vessels. The whole systemic circulation of the isolated trunk did not show any response to adenosine. When adenosine was infused into the ventral aorta of living trout, the gill resistance to blood flow was greatly increased.These results suggest that adenosine is able to control the arterious and venous blood pathways in the trout gills by modulating their vascular resistance.     

The ultrastructure of the blood vessels of Branchiostoma lanceolatum (Pallas) (Cephalochordata)

Summary The ultrastructure of the blood vessels of Branchiostoma has been studied using selected characteristic vessels as examples. It is shown that the vessels are a part of the original blastocoelic cavity and are delimited either by the basal laminae of adjacent epithelia or by connective tissue developed in the blastocoelic space. A brief account of the kinds of connective tissue is given. The observed contractility of some vessels depends on two types of contractile filaments situated in the basal part of the surrounding coelomic epithelia. Amoebocytelike cells are present in the blood. They may sometimes lie in contact with the wall of the vessels or with each other, but never form a typical endothelium with junctional complexes and a basal lamina of its own. Actually, there is no endothelium in any part of the vascular system. It is suggested that the term endothelium should be reserved for a closed cellular lining (with junctions) on the luminal side of the vessel wall, standing on a basal lamina of its own and forming a barrier for the exchange between blood and surrounding tissue. It is concluded that the principal structure of the vascular system of Branchiostoma is different from that of vertebrates, but the same as that of other coelomate invertebrates. The blood vessels in these animals are typically delimited directly by a basal lamina secreted by epithelia (epidermal, coelomic or intestinal) lying peripheral to this lamina, and a true endothelium is not present (with a few questionable exceptions).Abbreviations ac atrial cavity - ace atrial epithelium - ao aorta - ap atrial plexus - ax axon bundle - bc blood cell - bl basal lamina - bl ₁ basal lamina of intestinal epithelium - bl ₂ basal lamina of visceral coelomic epithelium - bl ₃ basal lamina of parietal coelomic epithelium - bl ₄ basal lamina of atrial epithelium - bll basement lamella - cf contractile filaments - co coelomic cavity - coe coelomic epithelium - coe _p parietal coelomic epithelium - coe _v visceral coelomic epithelium - ct dense connective tissue - dv longitudinal dorsal vessel - ep epidermis - epe epipharyngeal groove epithelium - epg epipharyngeal groove - fb fibroblast (?) - fi collagen fiber - fl fibril layer - go gonad - hd hemidesmosome - ie intestinal epithelium - in intestine proper - ip intestinal plexus - iv afferent intestinal vessel - ld liver diverticulum - lu vascular lumen - me myocoelic epithelium - ml muscle lamella - mp myoseptal plexus - ms myoseptum - my myomer - myc myocoelic cavity - nc notochord - ns notochordal sheath - ph pharynx - suc subchordal coelom - sv subintestinal vessel - svv segmental ventral vessel - vv longitudinal ventral vessel Supported by a grant from the Danish Natural Science Research Council     

Binding of Trypanosoma congolense to the Walls of Small Blood Vessels*

SYNOPSIS The mesenteric microvasculature was studied in rats and rabbits infected with Trypanosoma congolense. By examining vessels in the living animals, trypanosomes were observed to adhere to vessel walls by their anterior ends. It was evident from stained preparations of the vessels that the microcirculation contained 4–1400 times as many trypanosomes as were free in the cardiac blood. Parasites were more numerous in very small vessels than in larger vessels, and they were clustered in groups within the small vessels. The localization of T. congolense in the microvasculature is demonstrated and it is shown that this localization is established by attachment of the organism to the vessel wall.     

The bronchial tree and blood vessels of the Japanese monkey lung

The author injected various colored celluloid solutions into the bronchial tree and blood vessels of the lungs of five adult Japanese monkeys (Macaca fuscata) in order to prepare cast specimens. These specimens were investigated from the comparative anatomical viewpoint to determine whether the bronchial ramification theory of the mammalian lung (Nakakuki, 1975, 1980) can be applied to the Japanese monkey lung or not. The bronchioles are arranged stereotaxically like those of other mammalian lungs. The four bronchiole systems, dorsal, ventral, medial, and lateral, arise from both bronchi, respectively, although some bronchioles are lacking. In the right lung, the bronchioles form the upper, middle, accessory, and lower lobes, while in the left lung, the upper and accessory lobes are lacking and bi-lobed middle and lower lobes are formed. In the right lung, the upper lobe is formed by the first branch of the dorsal bronchiole system. The middle lobe is the first branch of the lateral bronchiole system. The accessory lobe is the first branch of the ventral bronchiole system. The lower lobe is formed by the remaining bronchioles of the four bronchiole systems. In the left lung, the middle lobe is formed by the first branch of the lateral bronchiole system. The lower lobe is formed by the remaining bronchioles. Thus, the bronchial ramification theory of the mammalian lung applied well to the Japanese monkey lung. The right pulmonary artery runs across the ventral side of the right upper lobe bronchiole. It then runs along the dorso-lateral side of the right bronchus between the dorsal bronchiole system and the lateral bronchiole system. On its way, it gives off branches of the pulmonary artery which run along the dorsal or lateral side of each bronchiole except in the ventral bronchiole system. In the ventral bronchiole system, the branches run along the ventral side of the bronchioles. The distributions of the pulmonary artery in the left lung are the same as those in the right lung. The pulmonary veins do not always run along the bronchioles. Most of them run on the medial or ventral side of the bronchioles. Some of them run between the pulmonary segments. In the right lung, these pulmonary veins finally form the right upper lobe vein, right middle lobe vein and the right lower lobe pulmonary venous trunk before entering the left atrium. However, the right accessory lobe vein runs on the dorsal side of the bronchiole and pours into the right lower lobe pulmonary venous trunk. In four cases out of the five examples, part of the right lower lobe veins pour into the right middle lobe vein, while the others enter the right lower lobe pulmonary venous trunk. In the left lung, the branches of the pulmonary veins finally form the left middle lobe vein and the left lower lobe pulmonary venous trunk.     

Structure,Ultrastructure, and Function of the Preoral Heart-Kidney in Saccoglossus kowalevskii (Hemichordata,Enteropneusta) Including New Data on the Stomochord

The heart-kidney of Saccoglossus kowalevskii, which is situated within the anterior preoral proboscis coelom (protocoel), consists of the stomochord, pericardium, heart sinus, and glomerulus. The stomochord, a diverticulum of the gut, is characterized by vacuolated epithelial cells surrounded by basal lamina and connective tissue. The pericardium, a myoepithelium, lies dorsal to the central heart sinus. Opening into the protocoel and connecting with the outside via the proboscis pore is the protocoel duct, which is, in part, composed of multiciliated absorptive epithelial cells. Perfusion of the dorsal trunk vessel with vital dyes reveals a rapid flow of blood into the glomerular blood vessels. Examination of the permeability characteristics of the extracellular matrix underlying the glomerular podocytes reveals the movement of iron dextran (mol. wt 5000 daltons) from the central heart sinus into the protocoel. Iron dextran uptake by glomerular cells and protocoel lining cells is demonstrated. These results suggest that vascular fluid is filtered by the glomerulus, producing a primary urine in the protocoel which may be modified as it passes over the peritoneum, through the protocoel duct, and out of the proboscis pore. New data concerning the morphology of the stomochord are presented. The controversial homology between the hemichordate stomochord and the chordate notochord is addressed.     

Mathematical modeling of the response of a resistive vessel to pressure

The response of small arterial vessels to internal pressure makes an essential contribution to autoregulation in the vascular bed. It is believed that free cytosolic Ca²⁺ concentration plays a pivotal role in the regulation of smooth muscle contractility and hence of the vascular lumen. A simple mathematical model of blood flow in a resistive vessel is suggested. The model is based on the experimental data obtained for cerebral arteries, but may be used for any other resistive vessel. The model not only describes the regulation of the vascular lumen by transmural pressure but also shows realistic behavior of the vessel radius and cytosolic [Ca²⁺] at different rates of pressure change. Possible variations in the radius along the vessel due to the Bayliss effect are considered.     

Vasculature of the head and respiratory organs in an obligate air-breathing fish,the swamp eel Monopterus (=Amphipnous) cuchia

Methyl methacrylate vascular corrosion replicas were used to examine the macrocirculation in the head region and the microcirculation of respiratory vessels in the air-breathing swamp eel Monopterus cuchia. Fixed respiratory tissue was also examined by SEM to verify capillary orientation. The respiratory and systemic circulations are only partially separated, presumably resulting in supply of mixed oxygenated and venous blood to the tissues. A long ventral aorta gives rise directly to the coronary and hypobranchial arteries. Two large shunt vessels connect the ventral aorta to the dorsal aorta, whereas the remaining ventral aortic flow goes to the respiratory islets and gills. Only two pairs of vestigial gill arches remain, equivalent to the second and third arches, yet five pairs of aortic arches were identified. Most aortic arches supply the respiratory islets. Respiratory islet capillaries are tightly coiled spirals with only a fraction of their total length in contact with the respiratory epithelium. Valve-like endothelial cells delimit the capillary spirals and are unlike endothelial cells in other vertebrates. The gills are highly modified in that the lamellae are reduced to a single-channel capillary with a characteristic three-dimensional zig-zag pathway. There are no arterio-arterial lamellar shunts, although the afferent branchial artery supplying the gill arches also supplies respiratory islets distally. A modified interlamellar filamental vasculature is present in gill tissue but absent or greatly reduced in the respiratory islets. The macro- and micro-circulatory systems of M. cuchia have been considerably modified presumably to accommodate aerial respiration. Some of these modifications involve retention of primitive vessel types, whereas others, especially in the microcirculation, incorporate new architectural designs some of whose functions are not readily apparent.     

The superficial vascular hyaloid system in the eye of the frogs,Rana temporaria and Rana esculenta

Summary The angioarchitecture of the superficial vascular hyaloid system (membrana vasculosa retinae) of the frog eye was studied by means of scanning electron microscopy of vascular corrosion casts. The terminal vessels form a single-layered sheath intimately adjacent to the vitreal side of the avascular retina. The hyaloid system is subdivided by the ventral venous trunk into three central areas: the dorsal, the temporo-ventral, and the naso-ventral area. Toward the ora serrata, the hyaloid system is bordered by an arterial ring, and by nasal and temporal venous branches forming more or less complete hemicircles. A vascular zone composed of several tongue-like sectors establishes an inter-connection between the peripheral vascular rings and the central areas of the fundus. The arterial blood is supplied from the arterial ring. The drainage of the hyaloid system is provided via two routes: (1) the Y-shaped ventral trunk collects blood from the central areas, (2) the two peripheral venous branches drain the tongue-like sectors. The vessels within the dorsal area follow preferentially a dorso-ventral meridional direction. This densely capillarized territory corresponds in localization to the area centralis retinae. The ultrastructure of microvessels of the hyaloid system is characterized by features typical for capillaries of the central nervous system.     

血管生长异常与流产的关系研究进展

微血管密度异常、血管生长因子(VEGF、PDGF等)及其受体表达异常通过一系列级联反应导致血管异常生长的结果。众多因子均和血管形成有关,在妊娠过程中对胎盘的血管发育有着重要的作用,导致滋养细胞的表型转换障碍、血管结构发育不良、血管生成受阻、血管数目减少,引起胎盘血管重铸障碍,胎儿胎盘单位灌注不足发生流产。研究表明许多自然流产的发生与胎盘组织中血管增生平衡和胎儿血液供应不足有密切关系,从而认为血管生长异常是导致流产的又一重要因素。随着研究的深入进展血管的异常生长与流产的关系是有确定关系的,对于血管生长异常所致的流产,抑制血管各种血管因子的形成、阻止其与受体结合,从而抑制血管的异常生长最终达到克服流产的发展,无异于把幸福带给更多的家庭,不仅是妇产科发展的里程碑,更是人类医学发展史上光辉的一笔。     

血管活动的个性化

机体内不同部位的血管功能活动均具有各自独特的性质,称为血管的个性,主要表现为不同器官或区域的血管对同一刺激的反应不尽相同,甚至截然相反。血管的这种生理学特征保证了血管能在不同部位与不同机能状态下作出不同反应,巧妙地完成血液循环系统的功能,满足机体不同部位的血供需要。血管活动的个性化是血管生理学中的一个重要问题,对这一问题的研究将有助于阐明血管活动的客观规律,对研究血管疾病的发生与发展也具有重要意义     

Morphology and tyrosine-hydroxylase immunohistochemistry of the systemic secondary vessel system of the blue catfish,Arius graeffei

Fish have a secondary vessel system which emerges from the primary vasculature via large numbers of coiled origins. The precise role of this vessel system is unknown. Vascular casting techniques and scanning electron microscopy reveal that the secondary vessels of the blue catfish, Arius graeffei, originate from dorsal, lateral, and ventral segmental primary arteries and from the caudal dorsal aorta. These vessels anastomose with each other to form larger secondary arteries which parallel the primary vessels for their entire length. Secondary vessels do not appear to form a capillary bed in the skin in A. graeffei as they do in some fish species. Coiled secondary vessel origins are abundant within the tunica media and adventitia of the primary vessels from which they emerge. The origins of the secondary vessels are surrounded by the extensive cytoplasmic processes of specialized endothelial cells. These processes extend for up to 6 μm into the lumen of the primary vessel. Ultrastructurally the coiled secondary capillaries consist of an endothelial cell tube which is surrounded by a single layer of pericytes. These endothelial cells extend large numbers of microvilli into the lumen of the coiled secondary capillary. Nerve terminals are commonly associated with the coiled secondary capillaries. Immunohistochemistry has revealed the presence of tyrosine-hydroxylase, an enzyme involved in catecholamine synthesis in nerve varicosities close to secondary vessels in A. graeffei. This vessel system could therefore be regulated by adrenergic nerves. © 1996 Wiley-Liss, Inc.     

Nervous system of the snail Helix aspersa

Summary The fine structure of vascular channels and amebocytes associated with the sheath of the infraesophageal ganglion of Helix aspersa, is described. The extracellular stroma of the sheath, together with the hemocoel and blood vessels, forms an interconnected system of pathways which appears to be involved in the transport of metabolites, amebocytes, hemocyanin and experimentally introduced opaque tracers. The hemocoel, blood capillaries and precapillaries are lined by a discontinuous layer of single muscle cells whose luminal aspect is covered by a lamina of extracellular material named the vascular coat. This coat consists of a ground substance that forms a basement membrane and filamentous elements some of which are collagenous. Gaps in the blood vessel wall seem to provide the main routes for the movement of cells and large molecules to the hemocoel. Tracer experiments have given support to the idea that a diffusion barrier may be absent at the sheath-ganglion junction. Amebocytes have phagocytic properties; they appear associated in groups or scattered singly within the extracellular space of the sheath and the lumen of blood vessels. Single amebocytes have features of mobile cells and may function in the transport of hemocyanin as well as other proteins.This work has been supported by the Rockefeller Foundation and grants NB 06662 (from the U.S. Public Health Service) and N-105 (from Conicyt, Santiago, Chile). The continuous advice and encouragement of Drs. R. W. Guillery and D. B. Slautterback are gratefully acknowledged.