Aging and endothelin-1 induced vascular contractions

Summary Contractions produced by endothelin-1 (0.3–30 nM) have been investigated in aorta, renal arteries and mesenteric arteries from 2- and 24-month-old Sprague-Dawley rats. In senescent rats the EC₅₀ values of endothelin-1 for aorta and renal artery were significantly increased (aorta: from 6.2 to 12 nM; renal artery: from 5.2 to 7.8 nM). For mesenteric artery the EC₅₀ value (4.3 nM) was unchanged by aging, whereas the maximal contractile response to endothelin-1 was enhanced (from 8.3 to 11.7 mN). In contrast, there was no significant age-related difference in the maximal endothelin-1 response of aorta and renal artery. The present data demonstrate a reduced sensitivity for aorta and renal artery and an enhanced maximal response to endothelin-1 in the mesenteric artery in senescent rats.     

Choroidal vascular repair: Scanning and transmission electron microscopy

Repair of the choroidal vasculature following laser photocoagulation in the rat was examined with vascular casts and correlated with observations on thin-sections. The regenerative process began at the periphery of the damaged area, starting from the surviving choriocapillaris and venules, and proceeding towards the center by means of recanalization of damaged vessels and growth of new ones. In small healed lesions the capillary bed was re-formed. It resembled the adjacent undamaged choriocapillaris morphologically but appeared to be less dense than the intact choriocapillaris when examined by scanning microscopy. In large lesions the capillary bed was re-formed at the periphery but not at the center. Also present at the edges of the large lesions were groups of new vessels which, when observed by scanning microscopy, appeared to extend in two directions; towards the subretinal space and towards the choroidal network. Another aspect of the repair process was the simultaneous occurrence of new vessel growth and capillary regression, which was observed both at the level of the choriocapillaris and at the foci of new vessels     

Effects of polysorbates and Cremophor EL on vascular responses in rat aorta

The effects of Tween 20, Tween 80, and Cremophor EL, surface active agents which are used for dispersion of water-insoluble substances, on vascular responsiveness were investigated using rat aortic rings. In high concentrations all these agents produced persistent contractions in aortic rings independent of the presence of endothelium. These contractions were not influenced by inhibitors of known endogenous contractile mediators. Incubation with these agents caused a concentration-dependent inhibition of the endothelium-dependent relaxant responses to acetylcholine in intact precontracted aortic rings. Endothelium-independent relaxations produced by sodium nitroprusside were not inhibited, but rather potentiated in the presence of Tween 80 (10^–1 ml/l). On the other hand, Tween 80 inhibited the contractile effects of 5-hydroxytryptamine, phenylephrine, and bradykinin significantly. The data suggests that these substances affect both endothelial cells and vascular smooth muscle.     

脂联素对1型糖尿病小鼠视网膜节细胞和血管的影响

目的:研究脂联素对1型糖尿病小鼠视网膜节细胞和血管的影响.方法:使用玻璃体腔内注射脂联素,腹腔内注射链脲佐菌素(STZ),免疫荧光,非侵入性眼压测量等实验方法,对1型糖尿病的视网膜节细胞数量的改变和血管形态的变化做研究.结果:1型糖尿病鼠脂联素组的眼压比1型糖尿病鼠对照组明显低(p＜0.01),而与正常鼠脂联素组相比明显升高(p＜0.01).与1型糖尿病鼠对照组相比,1型糖尿病鼠脂联素组的视网膜血管管径更粗一点.Brn3a+视网膜神经节细胞在1型糖尿病鼠脂联素组明显比1型糖尿病鼠对照组要多(p＜0.05),而与正常鼠脂联素组比较明显低一些(p＜0.01).结论:脂联素可明显改善1型糖尿病小鼠视网膜神经节细胞数量的下降,并可延缓视网膜血管形态的变化.APN有成为一种治疗糖尿病性视网膜病变的潜在可能性.     

Vascular reactivity in chronic Goldblatt two kidney-one clip hypertensive rats

Summary We studied the possible contribution of increased vascular reactivity in the chronic phase of Goldblatt two kidney-one clip hypertension. Vascular reactivity was evaluated in aortic strips from hypertensive rats (16 weeks after inducing hypertension) and age-matched control rats. The findings were: a) increased sensitivity to vasopressin in the aortic tissue of hypertensive rats, b) a similar response to angiotensin II, noradrenaline and KCl in hypertensive and control rats, and c) reduced maximal response to angiotensin II compared with other vasoconstrictors in both groups of rats. These results suggest a possible role for vasopressin in the chronic phase of this model of hypertension.The authors thank Ms Karen Shashok for revising the English style.     

Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ ERK1,2 and PI3K/Akt

The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial growth factor (VEGF) plays a central role in switching on the angiogenic phenotype during early cervical carcinogenesis. However, the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression, we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt. Received 23 November 2005; received after revision 10 January 2006; accepted 9 February 2006     

Neuronal control of brain microvessel function

Summary Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions.     

Molecular mechanisms of lymphatic vascular development

Lymphatic vasculature has recently emerged as a prominent area in biomedical research because of its essential role in the maintenance of normal fluid homeostasis and the involvement in pathogenesis of several human diseases, such as solid tumor metastasis, inflammation and lymphedema. Identification of lymphatic endothelial specific markers and regulators, such as VEGFR-3, VEGF-C/D, PROX1, podoplanin, LYVE-1, ephrinB2 and FOXC2, and the development of mouse models have laid a foundation for our understanding of the major steps controlling growth and remodeling of lymphatic vessels. In this review we summarize recent advances in the field and discuss how this knowledge as well as use of model organisms, such as zebrafish and Xenopus, should allow further in depth analysis of the lymphatic vascular system. Received 26 January 2007; received after revision 5 March 2007; accepted 29 March 2007     

Glycine-rich proteins as structural components of plant cell walls

Glycine-rich proteins (GRPs) have been found in the cell walls of many higher plants and form a third group of structural protein components of the wall in addition to extensins and proline-rich proteins. The primary sequences of GRPs contain more than 60% glycine. GRPs are localized mainly in the vascular tissue of the plant, and their coding genes provide an excellent system to analyze the molecular basis of vascular-specific gene expression. In French bean, the major cell wall GRP has been localized at the ultrastructural level in the modified primary cell wall of protoxylem. Immunological studies showed that it forms a major part of these highly extensible and specialized cell walls. Specific digestion of GRP1.8 from bean by collagenase suggests that it shares structural similarities with collagen. The protein is synthesized by living protoxylem cells as well as xylem parenchyma cells. After cell death, GRPs are exported from neighboring xylem parenchyma cells to the protoxylem wall, a rare example of protein transport between cells in plants. We propose that GRPs are part of a repair system of the plant during the stretching phase of protoxylem.     

Intra-vascular glucocorticoid metabolism as a modulator of vascular structure and function

The ability of glucocorticoids to directly alter arterial function, structure and the inflammatory response to vascular injury may contribute to their well-established link with the development of cardiovascular disease. Recent studies have emphasised the importance of tissue-specific regulation of glucocorticoid availability by the 11 β-hydroxysteroid dehydrogenase (11HSD) isozymes, which inter-convert active glucocorticoids and their inactive metabolites. The expression of both type 1 and type 2 11HSDs in the arterial wall suggests that prereceptor metabolism of glucocorticoids may have a direct impact on vascular physiology. Indeed there is evidence that 11HSDs influence glucocorticoid-mediated changes in vascular contractility, vascular structure, the inflammatory response to injury and the growth of new blood vessels. Hence, inhibition of 11HSD isozymes may provide a novel therapeutic target in vascular disease. Received 19 September 2005; received after revision 1 November 2005; accepted 25 November 2005     

Triphasic vascular effects of thiol compounds and their oxidized forms on dog coronary arteries

The vascular effects of 2-mercaptoethanol, cysteamine, L-cysteine, glutathione (GSH), cystamine and oxidized GSH (GSSG) on the isometric tension of isolated dog coronary arterial strips were examined, and these effects were compared with the triphasic response induced by dithiothreitol (DTT); a rapid and weak contraction (phase A), an intervening slow relaxation (phase B) and a slowly-developing strong contraction (phase C) which we previously reported. The responses of the arteries induced by 2-mercaptoethanol, cysteamine and L-cysteine consisted of phases A, B and C. The order of contractile potency (ED₅₀ of phase C) was DTTL-cysteine>2-mercaptoethanolcysteamine, while the order of relaxant potency (ED₅₀ of phase B) was DTT>cysteamine2-mercaptoethanol. GSSG and cystamine mainly produced relaxation, which corresponded to phase B. The phase C contraction was specific to the reduced forms of thiols, except for GSH, which produced only relaxation. The participation of endothelial cells was not essential for the contracting or relaxing effects of the thiol compounds. The phase C contraction was depressed by W-7, a calmodulin antagonist, while phase A was not. Therefore calmodulin-dependent protein kinases may participate in phase C, not in phase A.     

基于耗散率最小的“盘点”脉管网络构形优化

以有限温差传热和流动阻力引起的最小耗散率和耗散数为优化目标,在圆盘总面积和脉管网络总体积给定的条件下,对圆盘区域内一级、二级和三级脉管网络进行构形优化,得到耗散率和耗散数最小的各级脉管网络最优构形.结果表明当参数B1?10??时,在相同无量纲质量流率M*(1?M*?102)下,耗散率最小和熵产率最小的一级脉管网络最优构形有明显区别.对于二级脉管网络,当无量纲质量流率在1?M*?102范围内时,传热耗散和流动耗散大小相当,此时脉管网络最优构形随质量流率变化显著.在相同脉管网络总体积和圆盘半径条件下,相同无量纲质量流率时,一级、二级和三级脉管网络最小耗散数性能几乎相同;当无量纲泵功率*5?10(?1,2,3)?i W i时,随着脉管级数的增大,脉管网络最小耗散数减小,此时增加脉管网络的复杂度有利于提高脉管网络的性能.此外,还以复合耗散率为优化目标对脉管性能进行优化.优化结果可从传热优化角度为脉管系统设计提供参考.     

The role of VEGF receptors in angiogenesis; complex partnerships

Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development and homeostasis but also have profound effects on neural cells. VEGFs are predominantly produced by endothelial, hematopoietic and stromal cells in response to hypoxia and upon stimulation with growth factors such as transforming growth factors, interleukins or platelet-derived growth factor. VEGFs bind to three variants of type III receptor tyrosine kinases, VEGF receptor 1, 2 and 3. Each VEGF isoform binds to a particular subset of these receptors giving rise to the formation of receptor homo- and heterodimers that activate discrete signaling pathways. Signal specificity of VEGF receptors is further modulated upon recruitment of coreceptors, such as neuropilins, heparan sulfate, integrins or cadherins. Here we summarize the knowledge accumulated since the discovery of these proteins more than 20 years ago with the emphasis on the signaling pathways activated by VEGF receptors in endothelial cells during cell migration, growth and differentiation. Received 15 September 2005; received after revision 11 November; accepted 24 November 2005     

Sickle cell vasoocclusion: Many issues and some answers

The pathophysiology of sickle (SS) cell vasoocclusion is derived from the presence of hemoglobin S (HbS) which forms polymeric fibers in the deoxygenated state. Nevertheless, phenotypic expression of sickle cell disease (i.e., clinical severity) shows marked individual variations and is influenced by genetic modifiers such as epistatic effects of linked and unlinked genes. Furthermore, the polymerization of HbS is central but not the only event, and is more likely a consequence of disruptions of the steady state of flow. The available evidence indicates that the vasoocclusive crisis is a microcirculatory event in which multiple factors could be involved. We present a model of vasoocclusion as a two step process in which adhesion of deformable cells occurs first, followed by obstruction induced by less deformable SS cells. This review discusses, in addition, rheologic and microcirculatory behavior of SS erythrocytes and the interacting role of vascular factors, red cell heterogeneity, deoxygenation rates, and red cell-endothelial interactions in the pathophysiology of SS cell vasoocclusion.     

Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis

Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining ‘increased angiogenesis’ as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.Received 24 November 2004; received after revision 21 January 2005; accepted 2 March 2005     

Control of the cardiovascular system ofAplysia by identified neurons

The neural network that controls the cardiovascular system ofAplysia adapts cardiovascular function to a variety of different physiological and behavioral situations. It (1) coordinates the cardiovascular system with the renal and respiratory systems; (2) modifies both systemic and regional blood flow during food-elicited arousal and feeding; and (3) changes the tension of longitudinal vascular muscle to adapt the arterial tree to changes in body shape. Indirect evidence suggests that the cardiovascular control circuit may also play a role in maintaining homeostasis during egg laying. Several putative neurotransmitters, including acetylcholine, serotonin, R151 and R152 peptides, have been localized to identified neurons in this circuit.     

Inherent properties and statistics with individual particles in quantum mechanics

This paper puts forward the hypothesis that the distinctive features of quantum statistics are exclusively determined by the nature of the properties it describes. In particular, all statistically relevant properties of identical quantum particles in many-particle systems are conjectured to be irreducible, ‘inherent’ properties only belonging to the whole system. This allows one to explain quantum statistics without endorsing the ‘Received View’ that particles are non-individuals, or postulating that quantum systems obey peculiar probability distributions, or assuming that there are primitive restrictions on the range of states accessible to such systems. With this, the need for an unambiguously metaphysical explanation of certain physical facts is acknowledged and satisfied.     

Spasmin-like proteins in various ciliates revealed by antibody to purified spasmins ofCarchesium polypinum

Summary It was found that some ciliates,Stentor, Spirostomum andBlepharisma, which can contract rapidly like the stalks of Vorticellidae, have Ca²⁺-binding proteins that are very similar to spasmins, in the immunological sense. The presence of spasmins in other Protozoa and in some Metazoa was also investigated.