What Diabetes Mellitus Has Taught Us About Potential Treatments for Small Abdominal Aortic

3011 Cat: Miscellaneous

WHAT DIABETES MELLITUS HAS TAUGHT US ABOUT POTENTIAL TREATMENTS FOR SMALL ABDOMINAL AORTIC ANEURYSMS

S.D. Gertz1, L. Gavish1, Y. Mintz2, R. Beeri3, C. Rubinstein4, L.Y. Gavish1,

Y. Berlatzky4, L. Appelbaum5, D. Gilon3

1. Institute for Medical Research (IMRIC), The Hebrew University--Hadassah Medical School, Jerusalem, Israel

2. Department of Surgery, Hadassah University Hospital, Jerusalem, Israel

3. Department of Cardiology, Hadassah University Hospital, Jerusalem, Israel

4. Department of Vascular Surgery, Hadassah University Hospital, Jerusalem, Israel

5. Department of Radiology, Hadassah University Hospital, Jerusalem, Israel

Increased detection of abdominal aortic aneurysm (AAA) at early stages of growth (more than 80% of those diagnosed now are less than 3.5 cm maximum diameter), and the high rate of severe complications of urgent, open abdomen or endovascular surgical treatment have emphasized the need for less invasive strategies that target the pathogenetic mechanisms of progression and rupture. In sharp contrast to hypercholesterolemia, diabetes mellitus (DM) is negatively associated with AAA in experimental animal models and in epidemiological studies in humans. Whereas hypercholesterolemia favors an increased proteolytic state in the arterial wall, diabetes, through increased glycation of protein precursors and increased advanced glycation end products, facilitates matrix protein synthesis and increases covalent bonding of matrix proteins, rendering the wall less prone to proteolysis, decreasing the likelihood of aneurysmal dilatation and rupture. Recent studies from our laboratory have shown that Low Level laser (LLL) photobiomodulation, in the visible to near infrared range [780 nm] of the electromagnetic spectrum, used widely clinically for reducing pain and increasing wound healing, inhibits the development and progression of AAA in the angiotensin-II-infused, apolipoprotein-E-deficient mouse. The mechanism for this effect involves upregulation of collagen-rich fibrous matrix repair of transmedial defects in the aortic wall in the vicinity of aortic branch orifices. Reinforcement of the extracellular matrix in the aortic wall also explains the negative association between DM and AAA even though the underlying cellular mechanisms are different. In this talk, we discuss the use of minimally invasive photobiomodulation, and other options, for mechanism-based targeting and management of small, progressing aneurysms that are refractory to risk factor modification and pharmacological therapy in order to save the patient from the frequently severe consequences of urgent, obligatory, surgical or endovascular intervention.