Angiographic lesion characteristics can predict adverse outcomes after carotid artery stenting.

BACKGROUND: Carotid artery angioplasty and stenting (CAS) is an evolving and increasingly common endovascular treatment for carotid artery stenosis. Risk factors associated with an increased incidence of adverse periprocedural neurologic outcomes are being recognized. The goal of this study was to determine if certain angiographic lesion characteristics were predictive of higher risks of adverse outcomes. METHODS: A total of 421 patients who underwent 429 carotid artery stenting procedures between June 1996 and June 2005 for symptomatic or asymptomatic carotid stenosis, and in whom preoperative carotid angiograms and follow-up records were available for review, were selected from a prospectively maintained database. Demographic data and procedural variables were recorded, including the presence or absence of the use of a cerebral protection device. Angiograms were reviewed for the following carotid lesion characteristics: length of lesion, percentage of stenosis, ostial involvement, lesion ulceration, calcification, and presence of contralateral carotid occlusion. Periprocedural stroke and 30-day adverse event rates (stroke, myocardial infarction, and death) were recorded for each patient. RESULTS: The periprocedural all-stroke rate was 3.7%. Octogenarians had a higher incidence of 30-day adverse events at 10.0% vs 3.8% (P = .029). The incidence of periprocedural stroke was increased in lesions > or =15 mm long, at 17.0% (8 of 47) vs 2.1% (8 of 382; P < .001), and in ostial centered lesions, 7.1% (11 of 154) vs 1.8% (5 of 275; P = .007). Multivariate regression also identified these two variables as independently associated with 30-day stroke rate: lesion length > or =15 mm (odds ratio [OR], 6.38; 95% confidence interval [CI], 35 to 17.29) or ostial involvement (OR, 3.12; 95% CI, 3.12 to 8.36). Other variables, including lesion calcification, ulceration, degree of stenosis, or presence of contralateral occlusion, were not associated with adverse outcomes. When studied separately, the use of cerebral protection devices in 241 patients (56%) did not change our observed correlations between angiographic characteristics and adverse procedural events. CONCLUSIONS: Certain lesion characteristics on angiography, such as length and ostial location, can predict adverse outcomes. The indication for CAS should be carefully evaluated in these cases.

Ethanol inhibits pulse pressure-induced vascular smooth muscle cell migration by differentially modulating plasminogen activator inhibitor type 1, matrix metalloproteinase-2 and -9.

We investigated the effect of ethanol on the pulse pressure-induced expression of PAI-1 and MMP-2/9 in human smooth muscle cells (SMC). Human SMC were exposed to static or pulse pressure (25 mL/min; pulse pressure 106/50 mm Hg) conditions for 24 h in the absence or presence of ethanol (0.1-100 mM). SMC migration was then measured by Transwell migration assay. SMC exposed to pulse pressure demonstrated a significant increase in PAI-1 mRNA and protein expression (approximately 4-fold and approximately 3-fold) concomitant with a 3- and 8-fold increase in MMP-2 and MMP-9 protein, respectively. Ethanol dose-dependently inhibited the pulse pressure-induced SMC migration with complete inhibition observed at 20 mM. There was no effect of ethanol on basal PAI-1 or MMP-2/9 in SMC under static conditions. However, ethanol significantly enhanced the pulse pressure-induced PAI-1 mRNA and protein expression (2.2 +/- 0.52 fold and 2.5 +/- 0.27 fold, for 10 mM), respectively. In contrast, ethanol dose-dependently inhibited the pulse pressure-induced increases in MMP-9 protein and pro-MMP-9 activity and to a lesser extent MMP-2 mRNA and protein and pro-MMP-2 activity, with significant inhibition observed at 1 mM. These data provide a molecular mechanism mediating the inhibitory effect of ethanol on pulse-pressure-induced SMC migration and may be relevant to the cardioprotective effects of ethanol in vivo.

Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1{beta}-activated human endothelial cells.

The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1beta increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to approximately 900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1 secretion as determined by ELISA: 25 +/- 1%, 35 +/- 7%, and 65 +/- 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells. Similarly, EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1 mRNA expression. Experiments with actinomycin D demonstrated that EtOH decreased the stability of MCP-1 mRNA. In addition, EtOH significantly reduced NF-kappaB and AP-1 binding activity induced by IL-1beta and inhibited MCP-1 gene transcription. Binding of (125)I-labeled MCP-1 to its receptor (CCR2) on THP-1 human monocytic cells was not affected by EtOH treatment. Modulation of the expression of MCP-1 represents a mechanism whereby EtOH could inhibit atherogenesis by blocking the crucial early step of monocyte adhesion and subsequent recruitment to the subendothelial space. These actions of EtOH may underlie, in part, its cardiovascular protective effects in vivo.

Plasminogen activator inhibitor-1 deficiency enhances flow-induced smooth muscle cell migration.

INTRODUCTION: We determined the role of smooth muscle cell (SMC)-derived plasminogen activator inhibitor-1 (PAI-1) in the flow-induced SMC migratory response. MATERIALS AND METHODS: Wild type (wt) or PAI-1 knockout SMC were cultured in the absence or presence of endothelial cells (EC) under static or pulsatile flow conditions in a perfused culture system. SMC migration was then assessed by Transwell assay. RESULTS: Pulsatile flow significantly increased SMC PAI-1 mRNA and protein levels, approximately 4- and 3-fold respectively (n = 4, p < 0.05). In the absence, but not in the presence of EC, pulsatile flow significantly increased ( approximately 2.4-fold) the migration of wt SMC when compared to wt SMC cultured under static conditions. PAI-1 -/-SMC migration was significantly increased under flow conditions as compared to wild-type controls (334 +/- 22% vs. 237 +/- 11%, n = 6, p < 0.05). This flow-induced migration was significantly attenuated, but not completely inhibited, when PAI-1 -/-SMC were cultured in the presence of EC (147 +/- 13%, n = 6, p < 0.05). The flow-induced PAI-1 -/-SMC migratory response was partially inhibited by an anti-urokinase plasminogen activator (uPA) antibody (#1189), and completely inhibited by both 1189 and the matrix metalloproteinase (MMP) inhibitor BB3103. In parallel PAI-1 -/-SMC cells, there was a greater flow-induced increase in proMMP-2 activity as compared to wild-type control cells. Moreover, under both static and flow conditions, tissue inhibitors of matrix metalloproteinases (TIMP)-2 activity was reduced in these PAI-1-deficient cells as compared to wild-type controls. CONCLUSIONS: These results suggest that SMC PAI-1 plays a role in limiting flow-induced SMC migration and thus may be an important mechanism for controlling the process of vascular remodelling.

Predicting success after gastric bypass: the role of psychosocial and behavioral factors.

BACKGROUND: Success after bariatric surgery requires behavioral modification. This study analyzes outcomes after Roux-en-Y gastric bypass surgery performed by a single surgeon between 1994 and 2002, and correlates preoperative factors with long-term outcome. METHODS: A bariatric database has been maintained since 1994. Beginning in April 1997, patients completed preoperative and annual postoperative questionnaires that collected an array of psychosocial information. We hypothesized that certain attributes are predictive of success after surgery. RESULTS: Of the 243 patients in our database, 181 enrolled after 1997. A total of 149 were seen for follow-up at 1 year. Life Experiences Survey (LES) scores and sexual satisfaction improved significantly. Perceived obesity-related health problems, motivation unrelated to social distress about obesity, a Sense of Coherence (SOC) score >110, and an LES score <-1 each independently predicted better weight loss (P<.05). A history of sexual abuse correlated with poorer weight loss (P<.05). Patients with more confidants, multiple previous dieting attempts, and greater anticipated postoperative diet-related stress tended toward better weight loss, but these data did not reach significance. CONCLUSIONS: Intrinsic motivational factors appear to predict greater weight loss after surgery. Ongoing follow-up will help determine the utility of preoperative evaluations and the role of preoperative intervention in those with poor predictive factors.

Pulsatile flow-induced angiogenesis: role of G(i) subunits.

OBJECTIVE: Angiogenesis plays a key role in the growth and function of normal and pathological tissues. We investigated the effect of pulsatile flow on endothelial cell (EC) in vitro angiogenic activity. METHODS AND RESULTS: Bovine aortic ECs were exposed to "static" or "flow" (1.2 to 67.0 mL/min, shear stress 1.4 to 19.2 dyne/cm2) conditions for 2 to 24 hours. After exposure, angiogenesis was measured as tubule formation on Matrigel, and EC migration was assessed by filter migration assay. Pulsatile flow increased angiogenesis and EC migration in a temporal and force-dependent manner, with a maximal effect at 16 hours (13.2 dyne/cm2). Pertussis toxin completely inhibited the effect of pulsatile flow on angiogenesis and migration. Transfection of ECs with inhibitory mutants of the alpha subunit of G(i)1 or G(i)3, but not G(i)2, inhibited the flow-induced angiogenic response by 61+/-2% and 32+/-6%, respectively, whereas transfection with constitutively activated mutants of the alpha subunit of G(i)1 or G(i)3, but not G(i)2, increased the flow-induced response by 202+/-23% and 70+/-4%, respectively. In contrast, inhibition of Gbetagamma by the carboxy terminal fragment of beta-adrenergic receptor kinase overexpression increased the flow-induced response by 82+/-8%. CONCLUSIONS: These results suggest that pulsatile flow stimulates angiogenesis and that this effect is mediated by activation of G(ialpha)1 or G(ialpha)3, but not Gbetagamma, subunits.

Ethanol differentially modulates the expression and activity of cell cycle regulatory proteins in rat aortic smooth muscle cells.

The aim of this study was to determine the effect of ethanol on cell cycle events during the G(1) and S phases in cultured vascular smooth muscle cells (VSMC). Flow cytometric analysis for the DNA content in rat aortic VSMC indicated that following ethanol treatment, the cell population in the G(0)/G(1) phase increased; 57.8+/-1.6% vs. 72.3+/-1.2%, concomitant with a decrease in cells in the S phase; 12.7+/-1.4% vs. 3.67+/-0.6%, for control vs. ethanol, respectively. Western blot analysis on VSMC lysates demonstrated that ethanol (10-160 mmol/l) dose-dependently inhibited serum-induced retinoblastoma (pRb) hyperphosphorylation. While having no effect on Cdk2 protein expression, ethanol dose-dependently decreased (IC(50) approximately 60 mmol/l) Cdk2 activity, assessed by histone H1 phosphorylation. Furthermore, ethanol induced the expression of the cyclin-dependent kinase (Cdk) inhibitor p21(waf1/cip1), and inhibited the induction of cyclin A. These data demonstrate that modulation of the expression and activity of key cell cycle regulatory molecules may be a mechanism by which ethanol inhibits VSMC proliferation. These actions of ethanol may be relevant to its cardiovascular protective effect in vivo.