Hypothesis: Low Level Laser Prevents Abdominal Aortic Aneurysm in Angiotensin-II-Induced Apolipoprotein E-Deficient Mice by Inhibiting Decay of Smooth Muscle Cell Mitochondrial Membrane Potential

Infusion of angiotensin-II (Ang-II) into apolipoprotein-E-deficient (Apo-E^-/-) mice results in suprarenal abdominal aortic aneurysms (AAA) in up to 70 or 80% of cases. By high frequency ultrasound with correlative histomorphometry, we showed that phototherapy with low-level laser (LLL), a non-thermal, near-infrared radiation, used widely clinically for reduction of pain and acceleration of wound healing, prevents AAA in this mouse model by enhancing smooth muscle cell (SMC)-driven extracellular matrix reinforcement, and modification of the inflammatory response, at sites transmedial aortic defects that subtend the aneurysm formation. Earlier we found that LLL stimulates mitochondrial membrane potential (mitMP), suppresses the expression of the pro-inflammatory cytokine IL-1-beta, and disperses subnuclear promyelocytic leukemia protein, a cell-cycle checkpoint protein, in HaCaT human keratinocytes. Of particular importance, recent studies by others have shown that Ang-II causes decay in SMC mitMP with subsequent reduction in generation of ATP which is likely to dramatically reduce the capability for extracellular matrix synthesis. In this presentation we will provide the evidence suggesting that LLL prevents AAA in Apo-E^-/- mice by inhibiting Ang-II suppression of aortic SMC mitMP, thereby maintaining (or promoting) the intrinsic synthetic capabilities of the SMCs and, hence, matrix reinforcement of underlying transmedial aortic defects.