Interaction between oxygen and the blood vessel wall

Blood vessels in vivo respond to changes in the supply of oxygen relative to its demand. Whether the vessels which participate in such vasoregulatory responses are directly affected by oxygen remains an open question. Most studies of oxygen sensing by blood vessels have been carried out on strips, rings or segments isolated from relatively large vessels. These preparations are generally sensitive to oxygen from 0 mm Hg to some upper PO2 (10 to 240 mm Hg) whose value depends on experimental conditions. It appears unlikely that reduced energy production secondary to tissue hypoxia is directly responsible for the relaxation usually observed when PO2 is lowered below a critical value. Evidence that an oxygen-linked chemical mediator such as adenosine or prostacyclin is involved in contractile responses to lowered PO2 has been obtained. The site of action of oxygen could be anywhere within the vascular wall, but current evidence suggests a prominent role for the endothelial cells. At present extrapolation of these results to resistance vessels in vivo must be carried out with caution due to potential differences in the behaviour of microvessels relative to large vessels.     

Interaction of blood platelets with the vessel wall

This review summarizes current insights in the importance of endothelium in the interaction of platelets with the subendothelium. A greater part of the results described are obtained with the use of cultured vessel wall cells. The following subjects are discussed: (1) the pro- and antithrombotic properties of the endothelial cells; (2) the synthesis of subendothelium by the endothelial cells and the influence of the composition of the subendothelium on its reactivity towards blood platelets; (3) the effect of (purified) matrix and plasma proteins on the adhesion process, and (4) various abnormalities of platelet adhesion are discussed that lead to enhanced bleeding tendency or to increased thrombus formation.     

Effects of ionizing radiation on the blood vessel wall

PURPOSE: To study the biologic and clinical effects of ionizing radiation on blood vessels.MATERIALS AND METHODS: Data extracted from experimental and clinical reports and articles.RESULTS: Radiation-induced demise of endothelial cells is due to apoptosis. These cells are considered to be very radiosensitive. In vivo, however, the basal membrane might play a protective role. Early effects are characterized by swelling and shloughing of endothelial cells. Late effects are due to endothelial and smooth muscular cell proliferation. The underlying biologic mechanisms are little known. One hypothesis is the production of PDGF (platelet-derived growth factor) and FGF (fibroblast growth factor) by endothelial cells. Perivascular fibrosis might occur because of the TGF-beta production by endothelial cells and/or macrophages. Occurrence of late complications is probably multifactorial. Individual susceptibility to harmful effects of ionizing radiation, other vascular risk factors, and non optimal use of radiation treatment might contribute to the occurrence of late vascular complications. Modern radiotherapy using new techniques as the intensity modulation radiation therapy (IMRT) and the reduction of radiation doses and size of radiation fields should permit a dramatic reduction of vascular complications in cancer patients.CONCLUSIONS: Ionizing radiation treatments can lead to serious late vascular complications. A better understanding of the underlying biologic processes and newer radiation techniques might lead to fewer late complications in the very near future.     

Stromal and blood vessel wall invasion in well-differentiated hepatocellular carcinoma

Abstract: We examined hepatocellular carcinomas (HCCs) that were smaller than 2 cm in diameter. Ninety-nine nodules from 65 patients were removed for treatment. The nodules were divided into four types (A, B, C and D) according to the following criteria: first, the appearance of the margin of nodules, distinct or indistinct; and second, cellular atypia, uniform or multiple as “nodules in nodule”. In 45 indistinct margin nodules, 28 showed uniform atypia (type A) and 17 were of “nodules in nodule” (type B). As for 54 distinct margin nodules, 23 were “nodules in nodule” (type C) and 31 showed uniform atypia (type D). Cancer cell invasion was divided into three types: (1) stromal invasion into fibrotic tissue and/or portal tracts, (2) blood vessel wall invasion of portal veins or hepatic veins, and (3) tumor thrombus. The stromal and vessel wall invasion occurred almost at the same rate regardless of degree of atypia. This study shows that well-differentiated HCCs in which the cancer cells show only very slight atypia have the potential for metastasis to intrahepatic and other sites.     

Platelet-reactivity of isolated constituents of the blood vessel wall.

Collagens I and III, in fibrillar form, bound platelets equally well; both readily induced platelet aggregation. In contrast, collagens IV and V, although pretreated as collagens I and III to induce fibrillogenesis, failed to produce aggregation. No binding of platelets was detected. Lens capsule, containing collagen type IV in situ, was also inactive. Inactivity appears due to the lack of an appropriate quaternary structure since segment-long-spacing (SLS) aggregates of collagens IV and V, as of type I, induced aggregation. Elastin and its associated microfibrillar element did not aggregate platelets; some binding of platelets to elastin only was observed.     

Distribution and metabolism of angiotensin I and II in the blood vessel wall.

The demonstration of all components of the renin-angiotensin system in vascular tissue has raised questions as to the precise location of the local angiotensin II generation within the vascular wall. We investigated the metabolism of angiotensin I to angiotensin II in the vascular wall in the isolated rabbit thoracic aorta. Angiotensin I (3 x 10(-9) M) applied into the aortic lumen was partially converted to angiotensin II (14% after 60 minutes), but most of the luminal angiotensin I was degraded to peptide fragments or diffused as intact angiotensin I, peptide fragments, or both, into the vessel wall. Incubation studies with [3H]angiotensin I revealed that angiotensin I or angiotensin I fragments mainly diffused into the medial layer of the aorta and to a lesser degree into the adventitia and the endothelium. After removal of the endothelium, angiotensin II generation could no longer be detected. Addition of the angiotensin converting enzyme inhibitor ramiprilat (10(-7) M) to the incubation medium led to a complete blockade of angiotensin II generation by endothelial angiotensin converting enzyme. Our results underline the importance of the endothelium for conversion of angiotensin I to angiotensin II and provide evidence that conversion of angiotensin I to angiotensin II is predominantly achieved by endothelial cells. They also support the concept of an endocrine versus autocrine/paracrine renin-angiotensin system where the endothelium of the vasculature is the critical target site for angiotensin II production by both systems and, thus, the most important site for the actions of angiotensin converting enzyme inhibitors.     

Dynamics of shear-induced ATP release from red blood cells

Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in response to the increased shear stress inside arterial constrictions. Although shear-induced ATP release has been observed widely and is believed to be triggered by deformation of the cell membrane, the underlying mechanosensing mechanism inside RBCs is still controversial. Here, we use an in vitro microfluidic approach to investigate the dynamics of shear-induced ATP release from human RBCs with millisecond resolution. We demonstrate that there is a sizable delay time between the onset of increased shear stress and the release of ATP. This response time decreases with shear stress, but surprisingly does not depend significantly on membrane rigidity. Furthermore, we show that even though the RBCs deform significantly in short constrictions (duration of increased stress <3 ms), no measurable ATP is released. This critical timescale is commensurate with a characteristic membrane relaxation time determined from observations of the cell deformation by using high-speed video. Taken together our results suggest a model wherein the retraction of the spectrin-actin cytoskeleton network triggers the mechanosensitive ATP release and a shear-dependent membrane viscosity controls the rate of release.     

Cell-cell communication in the vessel wall

Intercellular communication between cells within the blood vessel wall plays an important role in the control of artery diameter. The endothelial cells lining the lumen of arteries can evoke smooth muscle hyperpolarization both by the release of a factor (EDHF) and by direct cell-cell coupling through gap junctions. Hyperpolarizing current can spread rapidly to cause widespread vasodilatation, and thus increase blood flow to that segment. In addition to the spread of current, small molecules, such as Ca2+, can also pass between cells, but at a much reduced rate. Instead of co-ordinating changes in diameter, intercellular Ca2+ signalling acts to amplify and, in special cases, modulate vascular responses. Together, direct cell-cell communication enables the blood vessel wall to act as a functional syncytium, which is influenced by surrounding tissues and nerves, and blood constituents.     

Multiple pathways of angiotensin production in the blood vessel wall: evidence, possibilities and hypotheses

In summary, multiple pathways of angiotensin production may exist in the blood vessel wall (Fig. 1), in addition to the well described renin--ACE enzymatic axis. It is not known whether these enzymatic pathways represent in vitro phenomena, or authentic in vivo alternate pathways which are activated only when the renin--ACE pathway is blocked, or whether they are operative at all times in the vessel wall. If these multiple pathways are functional, then the vascular angiotensin system may be very complicated, and may vary in different pathophysiological states. Future research in this area is likely to yield important and novel information on the in vivo pathways of production and function of vascular angiotensin.     

Apoptosis in inflammatory-fibroproliferative disorders of the vessel wall

Apoptotic cell death is a hallmark of inflammatory-fibroproliferative disorders of the vessel wall. Here, we review what is currently known about cell death within atherosclerotic and restenotic lesions. We also examine evidence suggesting that inflammatory cells contribute to the regulation of cell turnover within these lesions, and discuss the molecules expressed by vascular cells that modulate these processes. In toto, these studies suggest that apoptosis is prevalent in vascular lesions, controlling the viability of both inflammatory and vascular cells, and thus determining the cellular composition of the vessel wall.     

Additional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activator.

It is established that sympathetic neurons can synthesize, transport and store tissue plasminogen activator (t-PA) within axon terminals in the smooth muscle of vessel walls. Moreover, sympathetic excitations (e.g. physical and mental stress) are known to induce an acute release of t-PA into the circulation. However, relatively little is known about the nature and extent of sympathetic nervous system involvement in the release process. We inquired whether a chemical sympathectomy will alter the release of t-PA into the blood, and the intrinsic release of stored t-PA from isolated whole vessel explants. A long-term sympathectomy was induced in adult Sprague-Dawley rats by injection of guanethidine during a 5-week course. The destruction of ganglion neurons and vessel wall axons was verified immunohistochemically. t-PA release was assayed as the free activity in hind limb plasma and explant culture medium. Following sympathectomy: (i) the basal t-PA activity in plasma was 70% less than controls (2.92 +/- 1.96 versus 9.33 +/- 1.72 IU/ml; 相似文献