Restoration of renal allograft function via reduced-contrast percutaneous revascularization of transplant renal artery stenosis.

Transplant renal artery stenosis (TRAS), the most common vascular complication of kidney transplantation, can lead to heart failure, uncontrolled hypertension, and irreversible dysfunction of the transplanted kidney. Percutaneous revascularization can improve outcomes in well-selected patients with symptomatic TRAS, but the intervention itself poses risk to the transplanted kidney because of the quantities of nephrotoxic contrast solution that often are used. We report the case of a patient with TRAS who, 5 months after undergoing a kidney transplant, developed allograft dysfunction and heart failure that required hemodialysis.

Contemporary Management of Femoral Popliteal Revascularization.

Symptomatic peripheral artery disease of the femoral popliteal segment can be treated by surgical and endovascular revascularization, but controversy exists about the best approach. Conventional approaches to revascularization have focused on lesion anatomy to decide on bypass versus endovascular treatment, but advances in endovascular therapy make an endovascular-first approach increasingly feasible-either as a single approach or as an adjunct to short-segment bypass (ie, hybrid procedure). In this review, we discuss the medical, endovascular, and surgical treatment of femoral popliteal revascularization with a special emphasis on advances in percutaneous therapy.

Evaluation of the patient who presents with critical limb ischemia: diagnosis, prognosis, and medical management.

Patients with critical limb ischemia usually have severe atherosclerotic disease and are at a high risk of limb loss as well as major adverse cardiovascular events. The current article provides a description of the clinical presentation of patients with critical limb ischemia and also discusses the initial evaluation of these patients, including physical examination, use of noninvasive vascular tests, and other imaging modalities. An overview of the general management of these patients is also provided, including the identification of patients who benefit from revascularization or primary amputation, principles of wound care, and therapies for cardiovascular risk reduction.

Subcellular targeting and differential S-nitrosylation of endothelial nitric-oxide synthase.

Endothelial nitric-oxide synthase (eNOS) undergoes a complex pattern of post-translational modifications that regulate its activity. We have recently reported that eNOS is constitutively S-nitrosylated in endothelial cells and that agonists promote eNOS denitrosylation concomitant with enzyme activation (Erwin, P. A.

S-Nitrosation and regulation of inducible nitric oxide synthase.

The inducible isoform of nitric oxide synthase (iNOS) and three zinc tetrathiolate mutants (C104A, C109A, and C104A/C109A) were expressed in Escherichia coli and purified. The mutants were found by ICP-AES and the zinc-specific PAR colorimetric assay to be zinc free, whereas the wild-type iNOS zinc content was 0.38 +/- 0.

Receptor-regulated dynamic S-nitrosylation of endothelial nitric-oxide synthase in vascular endothelial cells.

The endothelial isoform of nitric-oxide synthase (eNOS) is regulated by a complex pattern of post-translational modifications. In these studies, we show that eNOS is dynamically regulated by S-nitrosylation, the covalent adduction of nitric oxide (NO)-derived nitrosyl groups to the cysteine thiols of proteins. We report that eNOS is tonically S-nitrosylated in resting bovine aortic endothelial cells and that the enzyme undergoes rapid transient denitrosylation after addition of the eNOS agonist, vascular endothelial growth factor.

VEGF induces S1P1 receptors in endothelial cells: Implications for cross-talk between sphingolipid and growth factor receptors.

Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that binds to S1P1 (EDG-1) receptors and activates the endothelial isoform of NO synthase (eNOS). S1P and the polypeptide growth factor vascular endothelial growth factor (VEGF) act independently to modulate angiogenesis and activate eNOS. In these studies, we explored the cross-talk between S1P and VEGF signaling pathways.