Division of Vascular Surgery

Basic Science Research

Control of Microcirculatory Exchange Function
Walter N Duran PhD

Inflammatory processes are characterized by an increase in microvascular permeability to macromolecules. Current information highlights controversial reports on the impact of nitric oxide (NO) in the control of microvascular permeability. Evidence in tissues and in isolated venules indicates that the activity of endothelial constitutive NO synthase (eNOS) increases microvascular permeability. To advance knowledge of the regulation of microvascular permeability, we are investigating three major hypotheses: 1) an eNOS-associated signaling cascade regulates microvascular transport; 2) molecular movement (translocation, trafficking) of eNOS from membrane to other cellular compartment(s) is a functionally and differentially important step in the endothelium-mediated regulatory mechanisms in vivo; and 3) eNOS signaling mechanisms regulate microvascular permeability. These studies are funded by the NIH.

Baseline distribution of eNOS (red) and caveolin (green) in human microvascular endothelial cells. Note preferential membrane-bound distribution of eNOS.

Pathophysiology of Chronic Venous Insufficiency
Peter J Pappas MD

Lower extremity venous hypertension causes varicose vein formation, leg pain, edema, itching, skin discoloration, ulcer formation and in severe cases, limb loss. These clinical symptoms constitute the disease known as chronic venous insufficiency (CVI). Our previous investigations demonstrated that pathologic tissue levels of TGF-ß1 were present in the lower extremity dermal matrix of CVI patients and that fibroblasts were the target cells of leukocyte derived TGF-ß1. Our preliminary data would suggest that molecular cross talk between SMAD transcription factors and the ERK MAP Kinase signaling cascade exists. Based on this data, we are currently studying how fibroblast generated matrix contraction may be regulated by molecular cross talk between ERK MAP Kinases and TGF-ß1 activated SMAD signaling. These studies were funded by the NIH and UMD Foundation grants.

Dermal fibroblasts cultured from lower extremity skin biopsies. In 2-3 weeks, patient fibroblasts can be seen migrating from the explant and populating the culture dish.

Non-invasive Imaging for Atherosclerosis
Brajesh K Lal MD

Cardiovascular diseases are the leading cause of death in the United States and atheroembolic stroke is a major contributor. Carotid plaque histology has identified several markers for unstable plaques at risk for disruption and stroke. These include intra-plaque hemorrhage, large lipid cores located close to the arterial lumen and fibrous-cap disruption. The specific aims of the project include 1) Identification of carotid plaque architecture by devising novel ultrasound B-mode and magnetic resonance imaging protocols and, 2) Identification of plaque tissue composition using ultrasound B-mode image analysis and proton magnetic resonance spectroscopy. These novel protocols are being performed on explanted carotid plaques and on patients undergoing carotid endarterectomy.

Imaging of the atherosclerotic carotid artery plaque using traditional angiography, and investigative B-mode image analysis high resolution magnetic resonance protocols with reconstructions.

Vascular Complications of Diabetes Mellitus Brajesh K Lal MD

Ischemic cardiovascular complications characterized by accelerated atherosclerosis, deficient collateralization and deficient post angioplasty re-endothelialization are the most common causes of mortality in diabetes mellitus (DM). Although DM is characterized by hyperglycemia, it is also accompanied by insulin resistance (Type II) or failing insulin secretion (Type I). Insulin is a potent anabolic hormone that promotes EC proliferation and prevents apoptosis by signaling through PI3k-Akt. This study explores the mechanisms by which high glucose concentrations may influence vascular EC proliferation and survival by modulating insulin signaling. The study is funded by the American College of Surgeons Faculty and UMD Foundation Grants.