Strategies for arterial graft optimization at the single-cell level.

Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell-cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts.

Diagnosis of coronary artery spasm by ergonovine provocation test of radial artery.

We investigated the sensitivity, specificity and safety of ergonovine provocation test of radial artery in the diagnosis of coronary artery spasm (CAS). The patients who came to our hospital for chest pain from January to June 2020 as well as had coronary stenosis < 50% and no radial artery stenosis, were enrolled in this study. These patients were divided into CAS group and control group after intracoronary ergonovine provocation test. All patients underwent ergonovine provocation test of radial artery, the inner diameter (D0 and D1) and the peak systolic velocities (PSV0 and PSV1) of the radial artery were measured by ultrasound before and after ergonovine provocation. The predictive value of ergonovine provocation test of radial artery for the diagnosis of CAS was analyzed using receiver operator characteristic (ROC) curve. There were 19 patients in the CAS group and 28 patients in the control group. Low density lipoprotein cholesterol and smoking rate were significantly higher in the CAS group than in the control group (all P < 0.05), but there were no significant differences in other items (P > 0.05) between the two groups. In the ergonovine provocation test of radial artery, degree of radial artery stenosis was significantly higher in the CAS group [41.50% (35.60%, 50.00%)] than in the control group [11.25% (5.15%, 23.00%)] (P = 0.000), but there were no siginificant differences in D0, PSV0 and PSV1 between the two groups (P > 0.05). The area under ROC curve of ergonovine (120 µg) provocation test of radial artery for the diagnosis of CAS was 0.912 with 95%CI: 0.792-0.975, P = 0.001, cut-off of 31%, specificity of 92.86% and sensitivity of 84.21%. The ergonovine (120 µg) provocation test of radial artery did not cause any adverse reactions. We concluded that the ergonovine provocation test of radial artery has high sensitivity, specificity and safety in the diagnosis of CAS.

Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial.

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.

Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease.

BACKGROUND: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. PATIENTS: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-ß (TGF-ß), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. RESULTS: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. CONCLUSION: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

Variability in gelatinase expression in the walls of vessels used as aortocoronary conduits may impact long-term graft patency.

BACKGROUND: An imbalance between the activity of matrix metalloproteinases (MMPs), particularly gelatinases, and tissue inhibitors of metalloproteinases (TIMPs) is considered as one of the mechanisms leading to aortocoronary graft failure. AIM: We aimed to assess the variability in gelatinase expression in the walls of aortocoronary conduits and to evaluate its impact on coronary artery bypass grafting (CABG) outcomes. METHODS: The study included 101 consecutive patients (61 men and 40 women) who underwent CABG. An immunohisto-chemical analysis of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression was performed on the cross-sections of the internal thoracic artery (ITA), radial artery (RA), and saphenous vein (SV). The histological findings were compared between patients with SV graft disease (SVGD[+] group) and those without occlusions in the SV (SVGD[-] group). RESULTS: The median MMP and TIMP expression was the weakest in the ITA wall. MMP expression was comparable between the RA and SV cross-sections, whereas TIMP expression was stronger in the RA than in the SV wall (p < 0.05). In most SV segments, but not in the arteries, immunostaining intensity for MMP was comparable to or stronger than for TIMPs. In the veins harvested from the SVGD(+) group, MMP-2 and MMP-9 tissue expression was more pronounced than in the SVGD(-) group. TIMP levels were comparable between groups. CONCLUSIONS: Imbalance in the metalloproteinase-to-inhibitor tissue expression in the vessel wall might predispose to graft failure. A stronger expression of TIMPs than MMPs in the arterial grafts might explain favourable long-term outcomes.

The Effect of Clopidogrel on the Response to Ischemia Reperfusion.

Reperfusion in the setting of acute ischemia is essential in limiting tissue necrosis. However, reperfusion itself is associated with significant adverse effects. There is animal evidence that platelets play a role in the adverse effects of ischemia and reperfusion (IR) injury. We examined whether clopidogrel would have favorable effects on endothelial dysfunction induced by an episode of IR. Using a parallel design, we administered clopidogrel 600 mg or matching placebo to normal volunteers (n = 20) 24 hours before an episode of IR. Flow-mediated dilatation (FMD, radial artery) was assessed before and after 20 minutes of upper arm ischemia. Following IR, there was a highly significant decrease in FMD in the placebo group (7.6% ± 1.3% vs 3.4% ± 0.1%; P < .001). In the clopidogrel group, there was no change in FMD post-IR (8.3% ± 0.8% vs 7.1% ± 1.2%; P = not significant). Following IR, FMD in the placebo group was significantly smaller than that observed in the clopidogrel group ( P < .01). Ischemia and reperfusion caused no change in plasma levels of biomarkers of inflammation (intercellular adhesion molecule 1, chemokine ligand 5, and interleukin 6) in either group. Therefore, a single dose of clopidogrel given 24 hours prior to an episode of IR had protective effects, limiting the adverse effects of ischemia on endothelial function.

Human splanchnic amino-acid metabolism.

Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L; P < 0.0001), citrulline was released (-36.1 ± 4.6 µmol/L; P < 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L; P = 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (-58.0 ± 4.4 µmol/L and -61.8 ± 5.2 µmol/L, P < 0.0001), and a smaller, but statistically significant release of tyrosine (-12.0 ± 1.3 µmol/L, P < 0.0001). The spleen only released taurine (-9.6 ± 3.3 µmol/L; P = 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine-citrulline pathway appears to be functional in the small intestine but not in the colon.

Alteration of type I collagen in the radial artery of patients with end-stage renal disease.

BACKGROUND: Cardiovascular disease is the leading cause of death in chronic kidney disease. Extracellular matrix remodeling is implicated in atherosclerosis development. This study investigated the effects and possible mechanism of type I collagen expression on radial artery elasticity in patients with end-stage renal disease (ESRD). METHODS: Sixty-five patients receiving forearm arteriovenous fistula in the Fourth Hospital of Hebei Medical University from January 2010 to December 2012 were enrolled in the study. The echo-tracking technique was used to measure radial artery 1-point pulse wave velocity (PWVß), and immunohistochemical staining was used to detect the expression of type I collagen and transcription factor CBFA1, a marker for calcification, in the radial artery. Uremic serum and serum from healthy volunteers of different concentrations were then used to treat the rat aortic vascular smooth muscle cells (VSMCs), reverse transcription polymerase chain reaction (PCR) was used to measure COL1A1 and CBFA1 transcription and a Western blot was performed to detect type I collagen expression in the rat aortic VSMCs. RESULTS: In patients with ESRD, increased COL1A1 expression was an independent risk factor for radial artery PWVß (P < 0.05) and was positively associated with that of CBFA1 (r = 0.573, P < 0.001). In the rat aortic VSMCs, serum from patients with ESRD upregulated COL1A1 and CBFA1 transcription as well as type I collagen expression in a concentration-dependent manner (P < 0.05). CONCLUSIONS: Type I collagen expression is an essential factor for radial artery elasticity dysfunction in patients with ESRD. Uremic toxins apparently induced a phenotypic transition of the rat aortic VSMCs, leading to increased type I collagen secretion and subsequent extracellular matrix remodeling.

[Expression and localization of the nuclear factor-κB classical signaling pathway in the radial artery of diabetic patients].

OBJECTIVE: To observe the expression and localization of the nuclear factor-κB (NF-κB) classic signaling pathway in the radial artery of the coronary artery bypass grafting (CABG) patients with diabetes and non-diabetes. METHODS: Samples of radial artery from 36 cases of diabetic and non-diabetic patients were randomly collected from January 2012 to December 2012.In the diabetic group there were 13 male cases, 5 female cases, with an average age of (69 ± 6) years.In non-diabetes group there were 13 male cases, 5 female cases, with an average age of (70 ± 6) years.HE staining techniques was used to test the morphology of radial artery. Immunohistochemical techniques was then used to test the expression and localization of key factors (inhibitor of kappa B kinase ß (IKKß), P50, P65, tumor necrosis factor-α (TNF-α) and endothelial nitric oxide synthase (eNOS)) in the NF-κB classical signaling pathway in the two groups of patients. RESULTS: The radial artery intima was signifiantly thickened in the diabetic patients when compared with non-diabetic patients by HE staining. And there wss a lot of inflammation and foam cell infiltration in the radial artery intima of the diabetic patients. Using immunohistochemical techniques the expression of IKKß, P50, P65 in diabetic group were obviously higher than non-diabetic group (4.4 ± 0.5 vs. 1.1 ± 0.6, 4.8 ± 0.7 vs. 1.2 ± 0.7, 4.2 ± 0.4 vs. 1.6 ± 0.7, t = 18.238, 15.052, 13.535, all P < 0.01).In the aspect of inflammatory cytokines, the expression of TNF-α and eNOS factors in diabeics group were significantly higher than non-diabetic group (5.5 ± 0.5 vs.1.4 ± 0.7, 3.3 ± 0.5 vs. 0.8 ± 0.4, t = 20.118, 16.764, all P < 0.01) also. And the five kinds of protein were mainly located in radial artery intima layer cells in diabetic patients. CONCLUSIONS: Expression levels of 5 key factors in NF-κB classic signaling pathway are significantly higher in radial artery intimal layer of diabetic patients than non-diabetic patient's. And Positive signals are more concentrated in the radial artery intima layer of cells.

The role of hemodynamic and vasoactive substances on hepatopulmonary syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a chronic hepatic complication characterized by defect in arterial oxygenation induced by pulmonary vascular dilatation and vasoactive substances in the setting of chronic liver disease (CLD). This study is to investigate the abnormality of hemodynamic and vasoactive substances in hepatopulmonary syndrome. PATIENTS AND METHODS: From September 2007 to September 2012, 58 patients with HPS in the General Surgery Department and Transplantation Center of Renji Hospital were enrolled for the case-control study. HPS patients enrolled were referred to as group H, CLD without HPS to as group C and case controls to as group N. Hemodynamic parameters of the systemic and pulmonary circulations as well as vasoactive substances in the radial and pulmonary arteries were measured in all patients. Univariate and multiple regression analysis were performed afterwards. RESULTS: The mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance and pulmonary vascular resistance (PVR) in HPS patients were significantly lower than those in CLD patients without HPS (p < 0.05). The nitrite-to-nitrate ratio (NO2-/NO3-), endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) in the radial and pulmonary arteries differed significantly among group H, group C and case controls (group N) separately (p < 0.05). The vasoactive intestinal peptide and 6-keto-prostaglandin-F1α in the radial and pulmonary arteries of group H were significantly higher than those in group N (p < 0.05). The NO2(-)/NO3(-) levels correlated negatively with PVR (r = -0.535, p < 0.05) and Endothelin-1 (r = -0.624, p < 0.05). CO (p < 0.05), CI (p < 0.05), SI (p < 0.05) and TNF-α (p < 0.05) level are considered significantly when performed with multiple regression analysis. CONCLUSIONS: The CO increases and PVR decreases in HPS patients. The abnormally elevated NO2-/NO3- level in the pulmonary circulation leads to pulmonary vasodilation. ET-1 may induce nitric oxide synthesis and correlated negatively with PVR in HPS. CO, CI, SI and TNF-α level are independent risk factors for HPS patients' survival.

[Expression and localization of vascular endothelial growth factor in the radial artery of the coronary artery bypass grafting patients with diabetes].

OBJECTIVE: To evaluate the quality of the radial artery for coronary artery bypass grafting (CABG) from patients with diabetes by observing the morphology of the radial artery and detecting the expression of vascular endothelial growth factor (VEGF) which may attribute to the long-term patency rate of the coronary artery bypass grafting. METHODS: Samples from 20 cases of diabetic and non-diabetic patients were prospective collected from June 2009 to December 2010. HE staining technique was used to test the morphology of radial artery through the observation of 20 cases of diabetic and 20 cases of non-diabetic patients who undergone CABG. The intimal thicken of the radial artery in the two groups of patients was compared. Western blot and immunofluorescence were then used to test the expression and location of VEGF in the two groups of patients. RESULTS: The radial artery endothelial thickening index and intima/media ratio were significantly higher in the diabetic patients when compared with non-diabetic patients (0.90 ± 0.28 vs. 0.29 ± 0.25, t = 7.27, P < 0.01; 0.90 ± 0.21 vs. 0.37 ± 0.18, t = 8.57, P < 0.01). The expression of VEGF in diabetic patients was significantly higher than non-diabetic patients as revealed by Western blot (1.20 ± 0.21 vs. 0.67 ± 0.15, t = 6.49, P < 0.01). Immunofluorescence showed that VEGF distributed in the cytoplasm of the endothelial cells of diabetic patients radial artery. CONCLUSIONS: Diabetic patient's radial artery intimal thickness is significantly higher than non-diabetic patient's. VEGF may be an important inflammatory cytokine which is leading the radial artery intima thickening in the diabetic patients. The choice of the radial artery grafts in diabetic patients for CABG should be careful.

Evidence that cranberry juice may improve augmentation index in overweight men.

The stiffening of arteries is a key step in atherogenesis leading to cardiovascular disease. It has been suggested that dietary polyphenols may be cardioprotective through possible favorable effects on oxidative stress and vascular function. The present study was undertaken in order to examine the effect of consuming low-calorie cranberry juice cocktail (CJC), a source of polyphenols, on arterial stiffness in abdominally obese men. We hypothesize that regular CJC consumption will reduce circulating oxidized low-density lipoproteins concentrations and have a beneficial impact on endothelial function. Thirty-five men (mean age ± SD: 45 ± 10 years) were randomly assigned to drink 500 mL CJC/day (27% juice) or 500 mL placebo juice (PJ)/day for 4 weeks in a double-blind crossover design. Augmentation index (AIx), an index of arterial stiffness, was measured by applanation tonometry of the radial artery and the cardiometabolic profile was assessed in each participant before and after each phase of the study. We found no significant difference in AIx changes between men who consumed CJC or PJ for 4 weeks (P = .5820). Furthermore, there was no between-treatment difference in changes in AIx responses to salbutamol (P = .6303) and glyceryl trinitrate (P = .4224). No significant difference was noted in other cardiometabolic variables between men consuming PJ or CJC. However, a significant within group decrease in AIx (mean decrease ± SE; -14.0 ± 5.8%, P = .019) was noted following the consumption of 500 mL CJC/day for 4 weeks. Our results indicate that the effect of chronic consumption of CJC on AIx was not significantly different from changes associated with the consumption of PJ. However, the significant within-group decrease in AIx following CJC consumption in abdominally obese men may deserve further investigation.

Comparative study on the histomorphology and molecular biology of radial artery conduits in patients with diabetes mellitus who underwent coronary bypass surgery.

We studied the impact of diabetes mellitus (DM) on the radial artery (RA) in 30 patients with DM and 30 non-diabetic patients undergoing coronary artery bypass grafting with autologous RA. RAs were recorded as normal if there was no cellular or stromal tissue between the endothelium and the internal elastic lamina. The RA was normal in 26.7% of diabetic and 76.7% of non-diabetic patients (p = 0.000298). Intimal thickness index and intima:media ratio were higher in the former than in the latter (p < 0.05; p < 0.05), with no significant difference in luminal narrowing (p > 0.05). Electron microscopy scores were lower in the non-diabetic group (p < 0.001); endothelial nitric oxide synthase (eNOS) protein expression and optical density were higher (p < 0.001). Von Willebrand factor and endothelin-1 messenger RNA (mRNA) levels were higher in the DM patients (p < 0.001). The quality of the RA in patients with DM was thus inferior to that in non-diabetic patients. Care should be taken when selecting RA as a conduit in patients with DM.

Radial construction of an arterial wall.

Some of the most serious diseases involve altered size and structure of the arterial wall. Elucidating how arterial walls are built could aid understanding of these diseases, but little is known about how concentric layers of muscle cells and the outer adventitial layer are assembled and patterned around endothelial tubes. Using histochemical, clonal, and genetic analysis in mice, here we show that the pulmonary artery wall is constructed radially, from the inside out, by two separate but coordinated processes. One is sequential induction of successive cell layers from surrounding mesenchyme. The other is controlled invasion of outer layers by inner layer cells through developmentally regulated cell reorientation and radial migration. We propose that a radial signal gradient controls these processes and provide evidence that PDGF-B and at least one other signal contribute. Modulation of such radial signaling pathways may underlie vessel-specific differences and pathological changes in arterial wall size and structure.

Prolonged antispasmodic effect in isolated radial artery graft and pronounced platelet inhibition induced by the inodilator drug, levosimendan.

Radial artery frequently develops spasm and requires vasodilator therapy during coronary artery bypass graft surgery (CABG). Levosimendan was recently shown to oppose 5-hydroxytryptamine-induced contraction of radial artery (RA) grafts. The aim of the present study was to explore whether levosimendan retains its vasodilatory capacity following in vitro pre-incubation of RA segments with the inodilator. A possible cumulative effect of the drug in human platelets was also studied. Human isolated RA segments were pre-incubated in 0.16 µmol/L levosimendan containing solution or in 0.9% NaCl, Bretschneider, 5% albumin and a 5% human serum protein solution (Biseko) as controls for 45 min. Contractions were induced by three consecutive administrations of 5-hydroxytryptamine (0.31 µM) 45, 90 and 120 min. after exchanging the pre-incubation solutions with Krebs-Henseleit solution, uniformly. Receptor-independent contractions (KCl, 80 mmol/L), endothelium-dependent (acetylcholine, 1 µmol/L) and independent relaxations (papaverine, 100 µmol/L) were also investigated. Washed human platelets were pre-incubated with levosimendan (0.06 µmol/L) for 2 or 15 min. and aggregated with thrombin (0.1 IU/mL). Contractions of RA grafts induced by 5-hydroxytryptamine were significantly smaller 45 min. and 90 min. after the replacement of levosimendan with Krebs-Henseleit solution. Biseko solution also decreased the contraction of the graft at 45 min. Contractions did not change in time following the pre-incubations of radial arteries with 0.9% NaCl, Bretschneider and 5% albumin solutions. The grafts remained intact as assessed by their maximum contractions and endothelium-dependent and endothelium-independent relaxations at the end of the investigations. Platelets revealed larger anti-aggregatory effect to levosimendan following the enhancement of the incubation time. Results indicate that the antispasmodic and anti-aggregatory effects of levosimendan cumulate in the vascular tissue and in platelets. The storage of RA with the inodilator before implantation may help to prevent the intraoperative spasm of the graft and also thrombotic occlusion during CABG surgery.

Endothelial integrity of radial artery grafts harvested by minimally invasive surgery--immunohistochemical studies of CD31 and endothelial nitric oxide synthase expressions: a randomized controlled trial.

OBJECTIVE: To compare the endothelial integrity of radial artery grafts harvested by minimally invasive surgery and arteries harvested conventionally for coronary artery bypass surgery (CABG) in 200 participants, who were assigned to interventions by using random allocation. METHODS: An immunohistochemical procedure with monoclonal antibodies was employed to estimate CD31 antigen and endothelial nitric oxide synthase (eNOS) expressions - markers defining endothelial integrity. RESULTS: The CD31 immunostaining revealed that the endothelial cell integrity of the minimally invasive harvested arteries was preserved in 76.1±7.4% of the circumference of luminal endothelium, which was similar to results obtained in conventionally harvested grafts (77.2±9.8%; not significant). On the other hand, eNOS immunostaining indicated that the endothelial integrity of the minimally invasive harvested grafts was preserved in 75.4±10.5% while in conventionally harvested grafts it was reduced to 42.4±14.5% of the total luminal endothelium circumference (P<0.05). CONCLUSIONS: The endothelial integrity of radial artery grafts harvested by minimally invasive surgery is better preserved than in the grafts obtained by the conventional manner. This could play an important role in improving graft patency and might represent a preliminary condition of stable functioning in coronary arterial bypasses.

Different expression of large-conductance calcium-activated K+ channels in human internal mammary and radial arteries.

AIMS: In this study, we investigated and compared the electrophysiological and molecular properties of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels between human internal mammary arteries (IMA) and radial arteries (RA). METHODS AND RESULTS: IMA and RA sections were obtained from 79 patients (including 9 females) undergoing coronary artery bypass graft surgery. We examined the effects of K(+) channel blockers tetraethylammonium (TEA), iberiotoxin (IBTX), and 4-aminopyridine (4-AP) on isolated smooth muscle cells (SMCs) using patch clamping. Both TEA (1 mM) and IBTX (0.1 µM) significantly decreased K(+) currents in IMA SMCs and RA SMCs, while 4-AP (1 mM) only had a weak effect. IBTX had a greater K(+)-blocking effect on IMA SMCs than on RA SMCs. Consistently, TEA and IBTX evoked significant constriction of both intact vascular rings. IBTX had a greater constrictor effect on IMA rings (18.5 ± 6.7%, n= 8) than on RA rings (10.6 ± 3.1%, n= 8), P< 0.05. RT-PCR and western blot analysis demonstrated that gene and protein expression of the α-subunit of BK(Ca) channels from IMA was greater than that from RA. CONCLUSION: The density of BK(Ca) channels is greater in human IMA than in RA resulting in greater BK(Ca) currents in SMCs from IMA. This may partly explain the finding of less spasm in IMA grafts than in RA grafts. Our results may be of value in determining the best anti-spasm agent to use peri-operatively.

Lead contributes to arterial intimal hyperplasia through nuclear factor erythroid 2-related factor-mediated endothelial interleukin 8 synthesis and subsequent invasion of smooth muscle cells.

OBJECTIVE: To validate the hypothesis that the toxic heavy metal lead (Pb) may be linked to cardiovascular diseases via the initiation of atherosclerosis, in vivo and in vitro studies were conducted. METHODS AND RESULTS: During the human study part of this project, serum Pb levels of healthy young women were correlated to carotid intima-media thickness. Multivariate logistic regression analyses showed that increased serum Pb levels were significantly associated with an increased intima-media thickness (P=0.01; odds ratio per SD unit, 1.6 [95% CI, 1.1 to 2.4]). In vitro, Pb induced an increase in interleukin 8 production and secretion by vascular endothelial cells. Nuclear factor erythroid 2-related factor-2 is the crucial transcription factor involved in Pb-induced upregulation of interleukin 8. Endothelial cell-secreted interleukin 8 triggered intimal invasion of smooth muscle cells and enhanced intimal thickening in an arterial organ culture model. This phenomenon was further enhanced by Pb-increased elastin synthesis of smooth muscle cells. CONCLUSIONS: Our data support the hypothesis that Pb is a novel, independent, and significant risk factor for intimal hyperplasia.

Connexin 43 expression is associated with vascular activation in human radial artery.

The gap junction protein, connexin 43 (Cx43) might be involved in the development of atherosclerosis. However, little is known about Cx43 expression in human arteries. We histologically analyzed the distal portions of radial (RA) and internal thoracic arteries (ITAs) obtained from 29 patients undergoing coronary artery bypass graft surgery. The medial smooth muscle cells of RA expressed Cx43, the intensity of which correlated with nuclear factor kappa B (NFκB) activation. In contrast, the expression of Cx43 in ITA did not correlate with NFκB activation. Cx43 appears to be involved in the pathogenesis of atherosclerosis especially in muscular arteries.