Stimulation of Eph-B4 prevents adaptive remodeling and preserves venous identity when veins are surgically placed into an arterial environment.

Reduced EphB4 expression is observed during vein graft adaptation and is associated with increased venous wall thickening. These findings suggest that EphB4 may mediate normal adult venous endothelial cell (EC) function and vein graft adaptation. We therefore tested the functional significance of EphB4 using EC with genetically reduced EphB4 signaling. EC were isolated from EphB4(+/+) and EphB4(+/-) mice. In vitro function was assessed through EC proliferation, migration, nitric oxide (NO) synthesis, and chemokine production. A mouse vein graft model was used to correlate in vitro findings with in vivo vein grafts. Smooth muscle cells (SMC) were subjected to proliferation and migration assays using EphB4(+/+) and EphB4(+/-) EC-conditioned medium. EphB4(+/-) EC exhibited diminished proliferation (P < 0.0001, n = 6), migration (P < 0.0001, n = 3), and NO production (P = 0.0012, n = 3). EphB4(+/-) EC had increased VEGF-A mRNA (P = 0.0006, n = 6) and protein (P = 0.0106, n = 3) as well as increased secretion of VEGF-A (P = 0.0010, n = 5), PDGF-BB (P < 0.0001, n = 6), and TGF-β1 (P < 0.0001, n = 6). EphB4(+/-)-conditioned medium promoted SMC proliferation (P < 0.0001, n = 7) and migration (P = 0.0358, n = 3). Vein grafts and EphB4(+/-) EC showed similarity with regard to VEGF-A and eNOS mRNA and protein expression. In conclusion, reduced venous EC EphB4 function is associated with a proangiogenic and mitogenic phenotype. EphB4(+/-) EC have increased secretion of SMC mitogens and reduced NO production that correlate with the thickened neointima formed during vein graft adaptation. These findings suggest that EphB4 remains active in adult venous EC and that loss of EphB4 plays a role in vein graft adaptation.

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Laparoscopy has become widely accepted as the preferred surgical approach in the management of benign and malignant colorectal diseases. Once considered a relative contraindication in patients with prior abdominal surgery (PAS), as surgeons have continued to gain expertise in advanced laparoscopy, minimally invasive approaches have been increasingly incorporated in the reoperative abdomen and pelvis. Although earlier studies have described conversion rates, most contemporary series evaluating the impact of PAS in laparoscopic colorectal resection have reported equivalent conversion and morbidity rates between reoperative and non-reoperative cases, and series evaluating the impact of laparoscopy in reoperative cases have demonstrated improved short-term outcomes with laparoscopy. The data overall highlight the importance of case selection, careful preoperative preparation and planning, and the critical role of surgeons' expertise in advanced laparoscopic techniques. Challenges to the widespread adoption of minimally invasive techniques in reoperative colorectal cases include the longer learning curve and longer operative time. However, with the steady increase in adoption of minimally invasive techniques worldwide, minimally invasive surgery (MIS) is likely to continue to be applied in the management of increasingly complex reoperative colorectal cases in an effort to improve patient outcomes. In the hands of experienced MIS surgeons and in carefully selected cases, laparoscopy is both safe and efficacious for reoperative procedures in the abdomen and pelvis, with measurable short-term benefits.

chronic renal failure, chronic obstructive pulmonary disease, CABG/V, and CAS (Table II). CAS carried a 2.5-fold increased risk of stroke or death vs CEA.Conclusions: CAS from 2004 to 2006 had a higher risk of stroke and death than CEA with and without CABG/V, even after adjustment for CMS high-risk criteria. Further risk-adjusted prospective and randomized analyses are needed before broad expansion of CAS.

Venous and arterial identity is predetermined in the embryo, with embryonic vessels expressing Eph-B4 differentiating into veins and vessels expressing ephrin-B2 differentiating into arteries. The specialized membrane organelles lipid rafts and caveolae serve as localized domains for proteins to interact with one another and play a role in signal transduction and vesicular trafficking. Several tyrosine kinase membrane receptors, including Eph-B1, have been colocalized to caveolae. These data suggest that caveolae and Eph receptors may have coordinated roles in determining vessel identity, not only during embryogenesis but perhaps also during adult vascular remodeling and angiogenesis.

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