Our research efforts are focused on abdominal aortic aneurysms (AAAs), a potentially life-threatening form of vascular disease. AAAs are characterized by chronic inflammation and destructive matrix remodeling within the aortic wall, leading to localized weakening, segmental dilatation, and eventual rupture. AAAs are relatively prevalent within the U.S. population, occurring in 2-8% of individuals over age 65. Although surgical repair of AAAs is an effective form of treatment for large aneurysms, the majority of AAAs are considered too small (and the risk of rupture thereby too low) to warrant elective surgical repair. Current treatment for small AAAs consists of surveillance imaging to detect aneurysm expansion, until a size is reached that would justify surgical repair. The goals of our work are twofold: (1) to understand the pathobiological mechanisms of aneurysm expansion such that pharmacological therapies might be developed to suppress progressive expansion of small AAAs, and (2) to identify circulating and imaging-based biomarkers of aneurysm disease that might help detect patients at particular risk for aneurysm expansion. Our current research activities thereby involve both laboratory-based studies and clinical investigations.
Our laboratory-based studies include delineation of the inflammatory mediators and matrix-degrading proteinases that promote aneurysm disease. We utilize experimental approaches ranging from the use of explanted human AAA tissues (obtained from the operating room) to a mouse model of AAAs induced by transient perfusion of the abdominal aorta with elastase. These approaches allowed us to first define the role of specific matrix metalloproteinases (MMPs) in AAAs, with the demonstration that MMP-9 is markedly overproduced in human AAA tissues and that mice deficient in MMP-9 are resistant to elastase-induced AAAs. Moreover, these studies led to the finding that treatment with MMP inhibitors, such as doxycycline, is an effective strategy in suppressing experimental AAAs. Additional studies have focused on inflammatory cytokines, such as interleukin-6 (IL-6) and angiotensin II (AngII), with the recent demonstration that both IL-6- and AngII-mediated signaling plays a pivotal role in experimental AAAs. Ongoing studies using the mouse model of AAAs therefore provide a robust experimental approach by which to define mechanisms and to identify therapeutic targets by which to potentially suppress AAAs in humans.
Our clinical studies take advantage of the high-volume vascular surgery service that exists at Barnes-Jewish Hospital and an interest in translating basic studies on the pathophysiology of AAAs to unresolved clinical problems. We are presently undertaking observational and longitudinal studies on circulating levels of proinflammatory cytokines (C-reactive protein, IL-6, MMP-9) in patients with AAAs, with comparisons to patients with occlusive carotid artery and lower extremity atherosclerosis. We have demonstrated that these biomarkers are consistently elevated to a much greater extent in patients with AAAs than other forms of vascular disease, reinforcing observations that aortic aneurysms are a chronic inflammatory condition. As these studies proceed it is our hope that identification of specific biomarkers for AAA expansion will provide novel tools for characterizing prognosis in these patients, thereby serving as a guide to future treatment approaches based on pharmacological and device-based treatments.
Thoracic outlet syndrome, TOS, minimally invasive surgical techniques and other treatment to patients with vascular disease including abdominal aortic aneurysms, thoracic aneurysms, renal aneurysms, carotid artery disease, arterial occlusive disease, brachiocephalic and upper extremity occlusive disease, aortoiliac and lower extremity occlusive arterial disease, and venous and lymphatic disease, axillary subclavian vein thrombosis.Also, aortic dissection, arterial fibrodysplasia, atherosclerosis, Buerger's Disease, claudication, deep venous thrombosis, DVT, diabetic vascular disease, arterial dissection, arterial embolization, fibromuscular dysplasia, FMD, hardening of the arteries, intermittent claudication, intestinal ischemia, mesenteric ischemia, minimally invasive vascular therapy, pediatric vascular care, pediatric vascular surgery, peripheral vascular disease, renal artery disease, renovascular hypertension, thoracic aneurysm, thoracoabdominal aneurysm, thrombolytic therapy, vascular disease, venous insufficiency, vascular disease in athletes