Abstract:
:Homeostasis around vascular endothelium is a function of the equilibrium between the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species (ROS). Within the vascular endothelium, NO enhances vasodilatation, reduces platelet aggression and adhesion (anti-thrombotic), prevents smooth muscle proliferation, inhibits adhesion of leukocytes and expression of pro-inflammatory cytokines genes (anti-inflammatory), and counters the oxidation of low density lipoprotein (LDL) cholesterol. A shift in the equilibrium that favours NO deficiency and ROS formation leads to endothelial dysfunction and cardiovascular disease. The synthesis of NO is catalysed by nitric oxide synthase and co-factored by tetrahydrobiopterin (BH4), nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), and flavin mononucleotide (FMN). The focus of this review is on endothelial nitric oxide synthase (eNOS), although we recognize that the other nitric oxide synthases may contribute as well. Levels of homocysteine and the active metabolite of folate, 5-methyltetrahydrofolate (5-MTHF), play a determining role in circulating levels of nitric oxide. We review endothelial nitric oxide bioavailabilty in relation to endothelial dysfunction as well as the therapeutic strategies involving the nitric oxide synthesis pathway. Although folate supplementation improves endothelial function, results from large clinical trials and meta-analyses on palpable clinical endpoints have been inconsistent. There are however, encouraging results from animal and clinical studies of supplementation with the co-factor for nitric oxide synthesis, BH4, though its tendency to be oxidized to dihydrobiopterin (BH2) remains problematic. Understanding how to maintain a high ratio of BH4 to BH2 appears to be the key that will likely unlock the therapeutic potential of nitric oxide synthesis pathway.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Yuyun MF,Ng LL,Ng GAdoi
10.1016/j.mvr.2018.03.012subject
Has Abstractpub_date
2018-09-01 00:00:00pages
7-12eissn
0026-2862issn
1095-9319pii
S0026-2862(17)30197-8journal_volume
119pub_type
杂志文章,评审abstract::In this paper we quantitatively investigate the hypothesis proposed by Michel (Exp. Physiol. 82, 1-30, 1997) and Weinbaum (Ann. Biomed. Eng. 26, 1-17, 1998) that the Starling forces are determined by the local difference in the hydrostatic and colloid osmotic pressure across the endothelial surface glycocalyx, which w...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1999.2177
更新日期:1999-11-01 00:00:00
abstract::The purpose of this study was to determine whether bidirectional flow exists in the sciatic vasa nervorum. Images obtained using high-frequency color Doppler ultrasound in duplex imaging mode (Vevo 2100) were studied retroactively. In Fig. 1 (left panel; rat 1), the color Doppler signal and flow-velocity waveforms are...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2014.05.008
更新日期:2014-07-01 00:00:00
abstract::Oxygen tension was recorded with double-barreled microelectrodes in the retina of anesthetized cats and monkeys. The oxygen tension (PO2) was often observed to undergo spontaneous irregular fluctuations with peak-to-peak amplitudes of about 3 to as much as 20 mm Hg. These fluctuations were observed only in the vascula...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(92)90103-v
更新日期:1992-07-01 00:00:00
abstract::Using the laser-Doppler method we measured blood flow on the nailfold skin to compare the reactivity of cutaneous microcirculation in three groups of normotensive subjects: 11 subjects with a familial predisposition to hypertension without a previous record of high blood pressure, 6 predisposed subjects with a previou...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.2000.2279
更新日期:2000-11-01 00:00:00
abstract::Alveolar epithelial and endothelial cell death caused by mechanical over-distension is likely to contribute to ventilator-induced lung injury (VILI). Consequently, the search for cytoprotective interventions is of interest. We investigated the effect of the mTOR inhibitor rapamycin on human pulmonary microvascular end...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2009.01.012
更新日期:2009-05-01 00:00:00
abstract::Oxidative stress, which is defined as an imbalance between proxidant and antioxidant systems, is the essential mechanism involving in the ischemic process. During the early stage of brain ischemia, reactive oxygen species (ROS) are increased. Increased ROS are thought of a consequence of brain ischemia and exacerbatin...
journal_title:Microvascular research
pub_type: 杂志文章,评审
doi:10.1016/j.mvr.2018.12.005
更新日期:2019-05-01 00:00:00
abstract::Endometriosis, the presence of endometrium-like tissue outside of the uterine cavity, is a common disease among women of reproductive age. Typical symptoms include abdominal pain and painful menstruation. In addition, endometriosis is associated with reduced fertility. Current treatment modalities, the surgical remova...
journal_title:Microvascular research
pub_type: 杂志文章,评审
doi:10.1016/j.mvr.2007.04.008
更新日期:2007-09-01 00:00:00
abstract::Synthetic big endothelin-1 (ET-1), a 39-residue precursor of ET-1, has been reported to elicit potent contractile action on helical strip specimens obtained from the porcine coronary artery, but its molar potency was found to be 140-fold lower than that of ET-1 [Saito, Y., Nakao, K., Mukoyama, M., Imura, H., 1990. Inc...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2006.04.007
更新日期:2006-11-01 00:00:00
abstract::Previous findings have shown that pulmonary fibroblasts are associated with preexisting holes in the endothelial and epithelial basal laminae through which neutrophils appear to enter and leave the interstitium as they migrate from capillaries to alveoli. To determine their role in neutrophil migration, fibroblast org...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1996.0029
更新日期:1996-05-01 00:00:00
abstract::The effect of mean blood velocity on thrombus formation parameters was studied using mesenteric vessels of white rats. An advanced phenomenological theory, explaining the relationship between mean blood velocity and thrombus growth rate, is presented. The qualitative analysis of theoretical and experimental data have ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1995.1002
更新日期:1995-01-01 00:00:00
abstract::We examined the influence of local cooling (-15 degrees C, 60 sec) on blood flow velocity in nailfold capillaries and on laser Doppler flux (LDF) at the fingertip in 12 patients with primary Raynaud's phenomenon (PRP) and 13 patients with secondary Raynaud's (SRP) in comparison with 10 health controls. Skin temperatur...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1993.1060
更新日期:1993-11-01 00:00:00
abstract::We determined whether the solvent drag reflection coefficient (sigma f) for total proteins of a canine perfused left lower lung lobe (LLL) preparation decreases at elevated venous pressures (Pv). We found that sigma f (estimated using the hematocrit-protein technique) remained constant at all Pv's (30-95 mm Hg) evalua...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(92)90006-b
更新日期:1992-01-01 00:00:00
abstract::Methods currently available for the examination of the retinal vasculature of laboratory animals have significant drawbacks. Fluorescein angiography of rodent eyes is hampered by a poor view of the peripheral retina and difficulty in performing fundus photography. Methods of staining or filling retinal vessels are unr...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1993.1042
更新日期:1993-09-01 00:00:00
abstract::Recent studies indicate that the human choroid has a considerable capacity to keep blood flow constant despite exercise-induced increases in perfusion pressure. The mechanisms underlying this vasoconstrictor response remain unclear. We hypothesized that pharmacological modulation of the autonomic nervous system may al...
journal_title:Microvascular research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0026-2862(02)00010-9
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:In the present study, we used a two-kidney-two-clip (2k2c) stroke-prone renovascular hypertension rat model (RHRSP) to investigate the protective effects of ligustrazine (TMP) on cerebral arteries and to examine PI3K/Akt pathway behavior under this protection. METHODS:The cerebral artery remodeling was induc...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2019.103938
更新日期:2020-03-01 00:00:00
abstract::The aim of this study was to evaluate whether streptokinase (SK) may produce beneficial effects at the level of microvascular circulation in addition to coronary recanalization. Twenty mongrel dogs weighing 28.4 +/- 4.6 kg were randomized to receive SK (16,000-72,000 U/kg) or 20 ml saline (control) in an open-chest an...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.2000.2236
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Angiogenin levels are increased in children and adolescent patients with type 1 diabetes, regardless of the extent of diabetic microangiopathy. However, little is known about the angiogenin concentrations in adults with type 1 diabetes. Thus we studied its level in middle aged subjects with the presence of d...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2012.08.005
更新日期:2012-11-01 00:00:00
abstract::Leukocyte margination in the vessels of the microcirculation has been attributed to a flow-dependent interaction with red cells. To determine the extent of this effect, experiments with human blood were done in 100- to 180-micron tubes to detect changes in cell distribution as a function of hematocrit and flow rate. U...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(84)90054-2
更新日期:1984-03-01 00:00:00
abstract:PURPOSE:Subcutaneous tissue is a promising site for cell transplantation; advantages include minimally invasive procedures and easy post-transplant monitoring. However, limited vascularity is the major known challenge. To address this challenge, a prevascularized graft bed is prepared in recipients. We aimed to establi...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2020.104070
更新日期:2020-11-01 00:00:00
abstract::Previous studies on mice have revealed that the Griffonia simplicifolia I (GSI) lectin selectively binds to capillaries in a number of microvascular beds. These observations suggest that the lectin might be a suitable microvascular marker for physiological studies of skeletal muscle, particularly when fluorescent visu...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(88)90022-2
更新日期:1988-11-01 00:00:00
abstract::We observed the retinal capillary pericytes of the rat in situ. Whole retinae were mounted, immediately post vivo, in a special tissue chamber for electronic light microscopy at high magnifications. Under electronic light microscopy the pericytes could be clearly distinguished from the endothelial cells. In addition, ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1998.2086
更新日期:1998-07-01 00:00:00
abstract::The large secreted glycoprotein thrombospondin-1 is a potent inhibitor of neovascularization in vivo. In order to better understand its mechanism of action, we have determined the full range of deficits thrombospondin can impose on cultured capillary endothelial cells. Exogenously added thrombospondin-1 blocked the ab...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1997.2015
更新日期:1997-07-01 00:00:00
abstract::A mathematical model of nonsteady-state fluid movement in the lung interstitium during hydrodynamic loading is evaluated. The model is based on experimental results obtained in isolated perfused canine lungs. The interstitium is treated as a porous phase with an elastic framework, able to relax; all resistance to flux...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(91)90071-i
更新日期:1991-07-01 00:00:00
abstract::In the present study, human myometrial microvascular endothelial cells (HMMEC) were cocultured with human vascular smooth muscle cells (VSMC) labeled with fluorescent dyes to examine their morphological interaction using confocal laser fluorescent microscopy. HMMEC and VSMC labeled with fluorescent green and red dyes,...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2005.04.008
更新日期:2005-07-01 00:00:00
abstract::Tetrahydroxystilbene glucoside (TSG) is the main water-soluble component in Polygonum multiflorum Thunb, and it has many cardioprotective effects. Although TSG is able to relax blood vessels, its relaxation of rat superior mesenteric arteries and the underlying mechanism of this process are not clearly understood. The...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2018.10.007
更新日期:2019-05-01 00:00:00
abstract::HPMECs were successfully isolated by differential trypsinization from peripheral lung lobes. The cells proliferated rapidly in EGM-MV with 10% FBS and were serially cultivated for more than 20 passages (1:4 split ratio) in vitro. Cells were characterized as endothelial based upon their cobblestone morphology, the pres...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1995.1064
更新日期:1995-11-01 00:00:00
abstract::Despite intensive study in the area of angiogenesis, relatively little is known about normal angiogenesis in adult animals. Preliminary studies using the Griffonia simplicifolia I (GSI) lectin as a microvascular marker indicated that capillary sprouting occurs in the clear "windows" of normal intact adult rat mesenter...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1994.1029
更新日期:1994-05-01 00:00:00
abstract::The mechanism by which macromolecular contents are concentrated during lymph transport was investigated in the collecting lymphatics of the mesentery of the rat. To examine changes in the concentration of lymph macromolecular tracer (fluorescein isothiocyanate-tagged dextran, MW 148,900) in the rhythmically contractil...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1997.2043
更新日期:1997-11-01 00:00:00
abstract::The role of VEGF during development and in pathology is well known, but its function in normal adult tissues is poorly understood. Adverse effects associated with the use of anti-angiogenic therapies targeting VEGF in human pathologies have begun to reveal potential functions of VEGF in quiescent vasculature. Further ...
journal_title:Microvascular research
pub_type: 杂志文章,评审
doi:10.1016/j.mvr.2007.03.004
更新日期:2007-09-01 00:00:00
abstract::Hypoxia-inducible factor-1 (HIF-1) orchestrates angiogenesis under hypoxic conditions mainly due to increased expression of such target genes as vascular endothelial growth factor (VEGF). Na+/H+exchanger-1 (NHE1), a potential HIF target gene product, plays a pivotal role in proliferation, survival, migration, adhesion...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2010.12.004
更新日期:2011-03-01 00:00:00