Shear stress and cyclic strain may suppress apoptosis in endothelial cells by different pathways.

Endothelial cells (ECs) are exposed to hemodynamic forces such as shear stress (SS) and cyclic strain (CS) in vivo. Alterations in these forces may stimulate EC growth and intimal hyperplasia, possibly by promotion of cell survival through inhibition of apoptosis. The authors examined the effect of SS and CS on inhibition of apoptosis and phosphorylation of Akt and its downstream target Bad in bovine aortic ECs in vitro. Arterial levels of laminar SS (14 dyne/cm(2)) or CS (10%) suppressed apoptosis due to serum withdrawal in EC; this suppression due to SS or CS was completely inhibited by phosphatidylinositol 3'-kinase (PI3K) inhibition. Phosphorylation of Akt in EC exposed to SS or CS was time dependent but with maximal stimulation at 30 min (SS) or 5 min (CS); SS- or CS-induced Akt phosphorylation was inhibited in the presence of PI3K inhibition. SS-induced, but not CS-induced, phosphorylation of Bad was inhibited by PI3K inhibition. These results suggest that hemodynamic forces suppress apoptosis in ECs via phosphorylation of Akt and that SS and CS differentially activate the downstream phosphorylation of Bad, possibly by stimulating an alternate pathway. This suggests an additional mechanism by which hemodynamic forces can differentially regulate transcription in ECs, and thereby possibly maintain the viability of normal endothelium.

Periprocedural drug therapy in carotid artery stenting: the need for more evidence.

Carotid artery stenting (CAS) is a widely accepted alternative for patients at high risk for carotid endarterectomy (CEA). However, the role, indications, and evidence for many pharmacologic agents that are used adjunctively in the periprocedural setting have not been established. Several drugs are commonly used before, during, and after CAS, but their uses have not been standardized. Large prospective cohort studies with good validity or randomized trials are needed to demonstrate efficacy, predict outcome, and determine the optimal use of these medications in patients undergoing CAS to improve patient care and obtain optimal outcomes. Several conclusions can be made: (1) dual-antiplatelet therapy (aspirin and clopidogrel) is commonly used for CAS; (2) the most commonly used regimen is aspirin 325 mg and clopidogrel 75 mg per day, but the optimal time of therapy is unknown; and (3) the dose and regimen of other agents used for CAS are not established.

Control of blood vessel identity: from embryo to adult.

Arteries and veins have been historically defined by the direction of blood flow and oxygen tension within the vessel, in addition to their functional, hemodynamic, and anatomical differences. It is now known that the molecular identity of these vessels is genetically predetermined, with specific molecular pathways activated during the development of arteries and veins. Eph-B4 is a determinant of venous differentiation and Ephrin-B2 is a determinant of arterial differentiation. Placement of a vein into the higher pressure and flow of the arterial circulation results in adaptation of the vein to the arterial environment. There is selective loss of Eph-B4 expression without induction of Ephrin-B2 expression during vein graft adaptation. These findings suggest that loss of venous identity is the crucial mechanism in vein graft adaptation and that developmentally critical determinants of vessel identity are plastic during adult life.

Adjunctive pharmacologic use in carotid endarterectomy: a review.

Although carotid endarterectomy (CEA) is now widely accepted as the surgical therapy for carotid stenosis, the role of and indications and evidence for many pharmacologic agents that are used adjunctively in the perioperative setting have not been conclusively established. Aspirin (acetylsalicylic acid) is the pharmaceutical agent that has been studied most extensively in conjunction with CEA; other than aspirin and dextran, the use of many agents before, during, and after CEA has not been standardized. Prospective randomized trials are still needed to demonstrate efficacy, predict outcome, and determine the optimal use of these medications in their adjunctive use during CEA to improve patient care and obtain optimal surgical outcomes.