The natural history of abdominal aortic aneurysms and their risk of rupture.
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Aged↗
Biomedical subjects
J T Powell
Publications and source records attributed to J T Powell.
Surgery for small asymptomatic abdominal aortic aneurysms.
BACKGROUND: An aneurysm is an abnormal ballooning of an artery. One site in which this occurs is in the abdominal aorta, which is the major artery running through the abdomen. Some abdominal aortic aneurysms (AAA) present as an emergency and require surgery; others remain asymptomatic. Treatment of asymptomatic aneurysms depends on a number of factors, one of which is size. The risk of rupture increases with aneurysm size. Large asymptomatic aneurysms (>6 cm diameter) are operated on; small aneurysms (<4 cm diameter) have regular ultrasound to monitor growth. OBJECTIVES: The objective of this review was to compare the mortality, quality of life and cost effectiveness of early surgical repair with routine ultrasound surveillance in patients with an AAA of between 4-6 cm diameter. SEARCH STRATEGY: Trials were identified through searching the Cochrane Peripheral Vascular Diseases Group trials register and the reference lists of relevant articles. The reviewers also contacted investigators in the field and hand searched recent conference proceedings. SELECTION CRITERIA: Randomised controlled trials in which men and women with asymptomatic AAA of diameter 4-6 cm were randomly allocated to early surgery, or ultrasound surveillance at least once every 12 months. Outcome measures had to include mortality, quality of life or financial costs. DATA COLLECTION AND ANALYSIS: Data were abstracted by one reviewer and checked by others. Due to the small number of trials at present no tests of heterogeneity or sensitivity analyses were performed. MAIN RESULTS: Only one trial, the UK Small Aneurysm Trial, fulfilled the criteria for inclusion. This trial found no differences in mortality between the early surgery and surveillance groups at two, four and six years following randomisation (six years Peto OR 1.01 [95% CI 0.77-1.31]). Mean health service costs were higher in the surgery than the surveillance group, difference 1,064 pounds per patient [95% CI 796-1332]. Quality of life remained similar in the two groups but early surgery patients thought they were healthier and had less pain one year after randomisation. There were not enough patients in the trial to allow analysis of subgroups by, for example, age or aneurysm size. REVIEWER'S CONCLUSIONS: The results from the one trial to date indicate that patients with asymptomatic AAA of 4-5.5 cm should normally have regular ultrasound surveillance accompanied by surgical intervention for aneurysms which grow rapidly (>1 cm per year) or reach 5.5 cm. The results are awaited of a major trial in progress in the USA.
Aortic Aneurysm, Abdominal↗
Risk factors for postoperative death following elective surgical repair of abdominal aortic aneurysm: results from the UK Small Aneurysm Trial. On behalf of the UK Small Aneurysm Trial participants.
BACKGROUND: In regional and population studies, the mortality rate within 30 days of elective surgical repair of abdominal aortic aneurysm is approximately 8 per cent. Identification of preoperative factors associated with this mortality risk is important for informing surgical policy and may suggest suitable preoperative interventions. METHODS: In the UK Small Aneurysm Trial, 820 patients aged 60-80 years underwent elective open surgical repair of an abdominal aortic aneurysm. The relationship between 30-day mortality rate and 13 prespecified potential prognostic factors was investigated. The value of a published clinical prediction rule was also evaluated. RESULTS: The postoperative mortality rate was 5.6 per cent overall (46 deaths in 820 patients). Postoperative mortality risk was significantly associated with older age (P = 0. 03), higher serum creatinine level (P = 0.002) and lower forced expiratory volume in 1 s (FEV1) (P = 0.003) in univariate analyses. Evidence of a relationship between age and postoperative death was weakened (P = 0.08) after adjustment for creatinine level and FEV1. The predicted postoperative mortality risk ranged from 2.7 per cent in younger patients with below average creatinine levels and above average FEV1, to 7.8 per cent in older patients with above average creatinine levels and below average FEV1. The published clinical prediction rule did not validate well on these data; observed risk did not correlate with predicted risk except for a small group of high-risk patients. CONCLUSION: Poor preoperative lung and renal function was strongly associated with postoperative death. Age was less important once these two important prognostic factors had been taken into account. The potential for preoperative improvement in lung and renal function to reduce postoperative mortality rates should be addressed in future studies.
Aged↗
Slowing the heart saves lives: advantages of perioperative beta-blockade.
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Adrenergic beta-Antagonists↗
Arterial flow induces changes in saphenous vein endothelium proteins transduced by cation channels.
OBJECTIVES: expression of leukocyte adhesins and proteins controlling thrombosis is likely to be an important determinant of graft patency early following vein bypass. We have previously demonstrated rapid increase in endothelial ICAM-1 and nitric oxide synthase (eNOS) concentrations in human saphenous vein exposed to arterial flow. The aim of this study was to investigate whether ion-channel-blocking drugs could alter these flow-induced changes. METHODS: human saphenous vein segments, freshly excised from patients, were placed in a validated in vitro circuit using flow conditions shown to simulate arterial or venous circulations for 90 min, in the presence or absence of ion-channel blockers. The concentrations of ICAM-1, VCAM-1, eNOS and tissue factor (TF) were assessed by quantitative immunohistochemistry in vein exposed to flow and compared with that in freshly excised vein from the same patient. The endothelial protein concentration was calculated as the mean area of staining as percentage of that for the control protein CD31, using computer-aided image analysis. RESULTS: after arterial flow conditions the area ratio of ICAM-1 increased from 21.4+/-1.4 to 44.6+/-2.0%, of eNOS increased from 50.0+/-5.6 to 70.1+/-5.0%, of VCAM-1 decreased from 16.6+/-3.4 to 3.6+/-1.0%, whereas TF staining area ratio was unchanged. Inclusion of the non-selective K(+)channel blocker, tetraethylammonium, in the arterial perfusion solution abolished all these arterial flow-induced changes. Inclusion of the K(+)ATP channel blocker, glibenclamide, selectively abolished the arterial flow-induced changes in ICAM-1 and VCAM-1. Inclusion of the calcium channel blocker, nifedipine, abolished the arterial flow-induced changes in eNOS and VCAM-1 but increased the TF staining area ratio from 3.0+/-0.4 to 8.5+/-0.7%, p=0.01. Inclusion of the stretch-activated cation-channel blocker, gadolinium, enhanced the arterial flow-induced increase in eNOS, but prevented the arterial flow-induced increase in ICAM-1. CONCLUSIONS: perfusion of veins under arterial flow conditions with gadolinium was associated with low endothelial concentrations of ICAM-1, VCAM-1 and TF, but high levels of eNOS. Such a concentration of endothelial proteins may be advantageous in newly implanted vein grafts. In contrast, nifedipine could have adverse effects by promoting increase in TF concentration.
Arteries↗
Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells.
It has been reported that fibrinogen may act as a bridging ligand, binding to intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells and to Mac-1 on THP-1 cells (a monocytic cell line) to increase adhesion. In this study, we investigated whether fibrinogen altered the expression of ICAM-1 and, thus, increased the adhesion of THP-1 cells to cultured human saphenous vein endothelial cells (HSVECs). Incubation of HSVECs with 0.3 to 4 micromol/L fibrinogen caused a time- and concentration-dependent increase in ICAM-1, as determined by ELISA. The 4- to 5-fold increase in ICAM-1 protein concentration in HSVECs stimulated by 4 micromol/L fibrinogen for 6 hours was concomitant with a 4- to 5-fold increase in ICAM-1 mRNA. This fibrinogen-stimulated ICAM-1 upregulation was associated with a 2-fold increase in THP-1 cell adhesion to HSVECs. The fibrinogen-derived peptide Bbeta15-42 bound to HSVECs (K(d) 0.18 micromol/L). Preincubation of HSVECs with Bbeta15-42, a neutralizing antibody to urokinase plasminogen activator (uPA), or the F(ab)(1) fragment of a monoclonal antibody to vascular endothelial cadherin significantly attenuated the increase in ICAM-1 stimulated by fibrinogen. Capillary electrophoretic analysis indicated that anti-uPA prevented the release of any fibrinopeptide B (Bbeta1-14) in cultures of HSVECs incubated with 4 micromol/L fibrinogen for 6 hours. Moreover, incubation of HSVECs with either fibrin monomer (1 micromol/L) or monoclonal antibodies to vascular endothelial cadherin (25 microg/mL) increased ICAM-1 protein concentration 3- to 4-fold. These findings indicate that cleavage of fibrinopeptide B from fibrinogen by endothelial uPA permits the exposed Bbeta15-42 sequence of fibrinogen to bind to vascular endothelial cadherin on HSVECs and to upregulate the expression of ICAM-1.
Amino Acid Sequence↗
Interaction of fibrinogen with saphenous vein endothelial cells stimulates tyrosine phosphorylation of cortactin.
Fibrinogen can engage diverse receptors on vascular cells, including ICAM-1. We have investigated the effect of fibrinogen on the tyrosine phosphorylation of cortactin, a cytoskeletal protein in human saphenous vein endothelial cells (HSVECs). Incubation of HSVECs with fibrinogen (0-4 microM) caused a concentration-dependent increase in the tyrosine phosphorylation of cortactin. Fibrinogen (4 microM) and fibrinogen fragment D (4 microM) caused 250% and >450% increase in tyrosine phosphorylation of cortactin respectively, but fibrinogen fragment E (50 kDa form) was ineffective. Preincubation of HSVECs with soluble ICAM-1 attenuated the response to fibrinogen. At physiological concentrations fibrinogen binds to receptors (probably including ICAM-1) on HSVECs, to increase tyrosine phosphorylation of cortactin.
Cells, Cultured↗
Fibrinogen up-regulates the expression of monocyte chemoattractant protein 1 in human saphenous vein endothelial cells.
High concentrations of fibrinogen in plasma have been associated with an increased risk of saphenous vein graft pathology. We have investigated the ability of fibrinogen to up-regulate the expression of monocyte chemoattractant protein 1 (MCP-1) in cultured human saphenous vein endothelial cells (HSVEC) isolated from saphenous vein. Increasing concentrations of fibrinogen (0-4 microM) stimulated a 20-fold increase in MCP-1 secretion within 4 h. Incubation of HSVEC with 2 microM fibrinogen for 4 h also caused a 2-fold increase in the MCP-1-to-glyceraldehyde-3-phosphate dehydrogenase mRNA ratio. The fibrinogen-mediated MCP-1 secretion fell to basal levels after preincubation of HSVEC with the complex of fibrinogen fragments D and E but remained unchanged after preincubation of HSVEC with either fibrinogen fragment E, s-ICAM-1 or the pentapeptide GRGDV. In contrast, fibrinogen fragment D acted as a potent inhibitor of fibrinogen-mediated MCP-1 secretion. Labelled fibrinogen fragment D bound to HSVEC with a K(d) of 6.5 microM. These findings indicate that fibrinogen, at physiological concentrations, uses an epitope on the fibrinogen D domain to bind to a receptor on HSVEC to up-regulate MCP-1 expression and secretion. This receptor seems to be distinct from intercellular adhesion molecule 1 and the integrins previously recognized as fibrinogen receptors.
Chemokine CCL2↗
Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms.
BACKGROUND: There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS: Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E2 (PGE2) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49+/-22 ng/g, 319+/-38 ng/mL, and 22+/-21 ng/mL, respectively. PGE2 inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC50, 23.2+/-3.8 and 23.6+/-4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE2 also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE2. In explants, indomethacin 10 micromol/L or mefenamic acid 10 micromol/L abolished PGE2 secretion and significantly reduced IL-1beta and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively, P=0.001. CONCLUSIONS: The adverse effects of PGE2 on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE2 synthesis could be an effective treatment to curtail aneurysm expansion.
Adolescent↗
Arterial flow conditions downregulate thrombomodulin on saphenous vein endothelium.
BACKGROUND: The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion. METHODS AND RESULTS: Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial flow conditions (mean pressure, 100 mm Hg, 90 cpm, approximately 200 mL/min) alter the concentration of proteins involved in regulating thrombosis at the vessel wall and (2) the influence of ion channel blockade on such effects. Concentrations of thrombomodulin and tissue factor were quantified by Western blotting (ratio of von Willebrand factor staining) and immunohistochemistry (as a percentage of CD31-staining area). Thrombomodulin concentrations after 90 minutes of venous and arterial flow conditions were quantified by immunostaining (68.9+/-4.8% and 41.0+/-3.0% CD31, respectively; P<0.01) and by Western blotting (1.35+/-0.20 and 0. 15+/-0.03 ratio of von Willebrand factor, respectively; P<0.01). The ability of endothelial cells to generate activated protein C also decreased from 62+/-14 to 19+/-10 ng. min-1. 1000 cells-1 (P=0.01). The significant reduction in thrombomodulin was attenuated if calcium was removed from the perfusate but not by external vein stenting. Inclusion in the vein perfusate of drugs that reduce calcium entry (including Gd3+, to block stretch-activated ion channels, and nifedipine) abolished the reduction in thrombomodulin concentration observed after arterial flow conditions. In freshly excised vein, negligible concentrations of tissue factor were detected on the endothelium and concentrations did not increase after 90 minutes of arterial flow conditions, although the inclusion of nifedipine caused the immunostaining to increase from 3.0+/-0.4% to 8.5+/-0.7% CD31 (P<0.02). CONCLUSIONS: In saphenous vein endothelium exposed to arterial flow conditions, there is rapid downregulation of thrombomodulin, sufficient to limit protein C activation, by a calcium-dependent mechanism.
Calcimycin↗
Uptake of tetracycline by aortic aneurysm wall and its effect on inflammation and proteolysis.
BACKGROUND: Proteolytic degradation of the aortic wall by matrix metalloproteinases (MMPs) is considered important in the pathogenesis of abdominal aortic aneurysms (AAAs). Many of these MMPs are inhibited by tetracycline derivatives, which may have the potential to retard aneurysm growth. METHODS: Patients undergoing elective repair of an AAA (n = 5) received an intravenous bolus of tetracycline (500 mg) on induction of anaesthesia and levels of tetracycline in serum, aneurysm wall and mural thrombus were assessed by microbiological assay. In a separate series of patients (n = 7) aneurysm biopsies were placed into explant culture (with and without tetracyline) and the accumulation of protein, hydroxyproline, MMP-9, interleukin (IL) 6 and monocyte chemoattractant protein (MCP) 1 in the medium was assessed by colorimetric assay or immunoassay. RESULTS: At aortic cross-clamping the median concentration of tetracycline was 8.3 microg/ml in serum, 2.9 microg per g tissue in aortic wall and zero in mural thrombus. Tetracycline inhibited, in a concentration-dependent manner, both MMP-9 and MCP-1 secretion (P = 0.022 and P = 0.018 respectively), but did not alter hydroxyproline or IL-6 secretion. At the highest concentration of tetracycline (100 microg/ml) median MMP-9 secretion was reduced from 27 to 5 ng/ml (P = 0.007) and median MCP-1 secretion was reduced from 50 to 10 ng/ml (P = 0.008). CONCLUSION: Tetracycline rapidly penetrates the aortic wall, but the concentration achieved may be insufficient to alter collagen turnover through limitation of MMP production or activity.
Aortic Aneurysm, Abdominal↗
The influence of indomethacin on the metabolism and cytokine secretion of human aneurysmal aorta.
INTRODUCTION: inflammation and proteolysis are important processes in the development of abdominal aortic aneurysms (AAAs). Prostaglandin E2 (PGE2) (a product of cyclo-oxygenase 2), other inflammatory mediators and proteolytic enzymes are produced in high quantities in the aneurysm wall. We developed an explant culture system for AAA tissue to assess the effects of potential drug therapies. METHODS: full thickness biopsies of human AAA were established in culture in the presence or absence of indomethacin (a cyclo-oxygenase-2 inhibitor). The conditioned medium was collected at 48 h intervals and analysed for products of collagen breakdown, matrix metalloproteinases, PGE2 and inflammatory cytokines. Explant viability was assessed by histology, glucose consumption, lactate dehydrogenase release and demonstration of protein synthesis in the tissue. RESULTS: nuclear morphology was maintained for 4 or more days and this, together with biochemical assays, indicated that AAA explants were viable in short-term culture. Indomethacin (10 microM) markedly reduced AAA explant production of prostaglandin E2 from 320 ng/ml to 3.3 ng/ml (p=0.028, n=6). Indomethacin also reduced the release of interleukin-1beta (IL-1beta) (from 166 pg/ml to 9.8 pg/ml, p =0.04, n=5) and interleukin-6 (IL-6) (from 119 ng/ml to 57 ng/ml, p=0.028, n=6), but had no effect on monocyte chemotactic protein 1 or matrix metalloproteinase-9 secretion. CONCLUSIONS: short-term explants of AAA are a novel method to assess the effects of drugs on aneurysm tissue. Indomethacin reduces the production of PGE2, IL-1beta and IL-6, suggesting that cyclo-oxygenase-2 inhibitors may control the inflammation in the aneurysm wall and potentially limit AAA growth.
Aorta, Abdominal↗
Evidence against prophylactic repair in small, asymptomatic abdominal aortic aneurysms.
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Aged↗
Outcome of femoropopliteal angioplasty.
OBJECTIVE: To assess prospectively the outcome of femoropopliteal angioplasty and investigate prognostic indicators of success. BACKGROUND: Percutaneous transluminal angioplasty is commonly used to treat symptomatic femoropopliteal stenoses or occlusions, but the durability of the procedure is uncertain. METHODS: Seventy-four consecutive patients treated by femoropopliteal angioplasty for intermittent claudication (43), rest pain (4), and tissue loss (27) were followed by assessment of symptoms, ankle-brachial pressure index (ABPI) to measure hemodynamic outcome, and duplex monitoring of velocity gradient at the angioplasty site to identify restenosis at 1 day and 3, 6, 9, and 12 months. Univariate comparisons, life table analysis, and backward stepwise regression were used to investigate factors predicting the symptomatic and hemodynamic outcome and restenosis. RESULTS: Technical success was obtained in 67 patients (91%); failure occurred in 7 patients. At 1 year, a successful symptomatic outcome was achieved in 35 patients (51%), hemodynamic success was achieved in 41 patients (58%), and restenosis developed in 39%. ABPI at 24 hours after angioplasty was the most significant variable predicting a symptomatic outcome, hemodynamic outcome, and restenosis at 12 months. Life table analysis demonstrated that in 24% of patients with a 24-hour ABPI > or =0.9, restenosis developed by 12 months, compared with 64% of patients with a 24-hour ABPI <0.9. CONCLUSION: Only half of the patients treated by femoropopliteal angioplasty had symptomatic improvement at 1 year, raising concern about the cost-benefit ratio of this procedure. Restoration of ABPI to >0.9 predicted a favorable outcome.
Angioplasty, Balloon↗
Risk factors for aneurysm rupture in patients kept under ultrasound surveillance. UK Small Aneurysm Trial Participants.
OBJECTIVE: To investigate risk factors associated with aneurysm rupture using patients randomized into the U.K. Small Aneurysm Trial (n = 1090) or monitored for aneurysm growth in the associated study (n = 1167). SUMMARY BACKGROUND DATA: The U.K. Small Aneurysm Trial has shown that ultrasound surveillance is a safe management option for patients with small abdominal aortic aneurysms (4.0 to 5.5 cm in diameter), with an annual rupture rate of 1%. METHODS: In the cohort of 2257 patients (79% male), aged 59 to 77 years, 103 instances of abdominal aortic aneurysm rupture were identified during the 7-year period of follow-up (1991-1998). Almost all patients (98%) had initial aneurysm diameters in the range of 3 to 6 cm, and the majority of ruptures (76%) occurred in patients with aneurysms > or =5 cm in diameter. Kaplan-Meier survival and Cox regression analysis were used to identify baseline risk factors associated with aneurysm rupture. RESULTS: After 3 years, the annual rate of aneurysm rupture was 2.2% (95% confidence interval 1.7 to 2.8). The risk of rupture was independently and significantly associated with female sex (p < 0.001), larger initial aneurysm diameter (p < 0.001), lower FEV1 (p = 0.004), current smoking (p = 0.01), and higher mean blood pressure (p = 0.01). Age, body mass index, serum cholesterol concentration, and ankle/brachial pressure index were not associated with an increased risk of aneurysm rupture. CONCLUSIONS: Within this cohort of patients, women had a threefold higher risk of aneurysm rupture than men. Effective control of blood pressure and cessation of smoking are likely to diminish the risk of rupture.
Aged↗
Rapid changes in the coagulant proteins on saphenous vein endothelium in response to arterial flow.
Healthy endothelium provides a nonthrombogenic surface. In this study the authors investigated the effect of arterial flow on the saphenous vein endothelial expression of proteins controlling thrombosis. Human saphenous vein segments, freshly excised from patients, were placed in a validated in vitro circuit with flow conditions shown to simulate arterial or venous circulations. In separate experiments, placement of an external polytetrafluoroethylene (PTFE) stent was used to differentiate the effects of pulsatile wall deformation and shear stress, while addition of drugs to the vein perfusate allowed study of the role of ion channels in transducing the response of the vein to arterial flow. Endothelial concentrations of thrombomodulin, nitric oxide synthase, tissue factor, and tissue plasminogen activator were assessed by quantitative immunohistochemistry and Western blotting of endothelial cell lysates, in paired vein samples, in comparison to control proteins. Arterial flow conditions caused a rapid and significant reduction in the endothelial concentration of thrombomodulin: The immunostaining area decreased from 80.1 +/- 7.0 to 48.3 +/- 5.0 and 32.9 +/- 3.0% at 45 and 90 minutes respectively, p = 0.01. These findings were confirmed by Western blotting. The reduction in thrombomodulin concentration was unaffected by eliminating vein wall deformation by placement of an external PTFE stent or by including the K+ channel blocker tetraethylammonium (TEA) in the vein perfusate. In contrast, thrombomodulin concentrations remained high when blockers of stretch-activated cation and calcium channels were included in the vein perfusate. The endothelial concentration of nitric oxide synthase increased after 90 minutes of arterial flow and this change was abolished when TEA was included in the vein perfusate. Arterial flow induced rapid changes in saphenous vein antithrombotic proteins. Different cation channels mediated the flow-induced changes in thrombomodulin and nitric oxide synthase.
Blood Flow Velocity↗
Does nibbling or grazing protect the peripheral arteries from atherosclerosis?
BACKGROUND: It has been suggested that frequent food intake is metabolically advantageous. We investigated whether meal frequency was associated with the development of peripheral arterial disease among smokers. DESIGN: Hospital-based case-control study of smokers, recruited from outpatient clinics and inpatient wards at two London teaching hospitals. METHODS: Two-hundred and ninety-one smokers, newly referred with peripheral arterial disease (cases) and 828 age- and sex-matched smokers without smoking-related disorders and with negative Rose questionnaire responses for intermittent claudication (controls) were recruited. All cases and controls completed a validated questionnaire concerning dietary habits. Odds ratios for peripheral arterial disease in association with several dietary variables were calculated, after adjustment for confounding variables. RESULTS: After adjustment for age, sex, pack-years of smoking, diabetes, hypertension and body mass index, the odds ratio for peripheral arterial disease among those smokers eating between meals (grazing) compared with those who did not, was 0.54 (95% confidence interval 0.42-0.83; P < 0.001). Among cases and controls, grazing was also associated with significantly lower plasma cholesterol concentrations (median 5.67 mmol/l in grazers compared with 6.08 mmol/l in non-grazers; P < 0.001) in those with apparently similar overall fat intakes. Neither plasma lipoprotein (a) nor fibrinogen concentrations varied with meal frequency. CONCLUSIONS: In smokers, grazing was associated with a reduced risk of developing symptomatic peripheral atherosclerosis. This is the first study to demonstrate the apparent benefits of grazing on a cardiovascular end-point.
Aged↗
Human saphenous vein endothelial cells express a tetrodotoxin-resistant, voltage-gated sodium current.
Whole-cell patch-clamp electrophysiological investigation of endothelial cells cultured from human saphenous vein (HSVECs) has identified a voltage-gated Na+ current with a mean peak magnitude of -595 +/- 49 pA (n = 75). This current was inhibited by tetrodotoxin (TTX) in a concentration-dependent manner, with an IC50 value of 4.7 microM, suggesting that it was of the TTX-resistant subtype. An antibody directed against the highly conserved intracellular linker region between domains III and IV of known Na+ channel alpha-subunits was able to retard current inactivation when applied intracellularly. This antibody identified a 245-kDa protein from membrane lysates on Western blotting and positively immunolabeled both cultured HSVECs and intact venous endothelium. HSVECs were also shown by reverse transcription-polymerase chain reaction to contain transcripts of the hH1 sodium channel gene. The expression of Na+ channels by HSVECs was shown using electrophysiology and cell-based enzyme-linked immunosorbent assay to be dependent on the concentration and source of human serum. Together, these results suggest that TTX-resistant Na+ channels of the hH1 isoform are expressed in human saphenous vein endothelium and that the presence of these channels is controlled by a serum factor.
Adult↗