Abstract 1667: Biglycan Deficiency Attenuates Vascular Smooth Muscle Cell Proliferation and Migration Protecting against Hypertrophy
Biglycan is a small proteoglycan primarily synthesized by vascular smooth muscle cells. Its expression is altered in disease states, with increased expression in atherosclerotic and restenotic lesions. Biglycan is thought to play roles in the control of collagen deposition and the regulation of cytokine activity, and has been shown to stimulate vascular smooth muscle cell proliferation. Over-expression of biglycan in vascular smooth muscle cells in vivo was shown to cause vascular hypertrophy and fibrosis. To test the hypothesis that biglycan deficiency would be protective against vascular injury, biglycan deficient (bgn-/-) mice and their wild-type littermate controls were subjected to wire-injury in the femoral artery. There was no difference in the femoral wall thickness between bgn-/- and wildtype mice in the uninjured femoral artery. However, evaluation of the femoral arteries 4 weeks after the injury revealed decreased arterial wall hypertrophy in bgn-/- mice compared to littermate controls (p<0.05). To determine if biglycan deficiency decreased cell proliferation and/or migration, vascular smooth muscle cells were isolated from bgn-/- mice and their wild-type controls. In contrast to wildtype cells, bgn-/-smooth muscle cells showed significantly reduced proliferation (p<0.001) in response to serum, evident by 2 days after plating. Furthermore, bgn-/- cells had decreased migration compared to the wild-type cells, as analyzed by a scratch wound assay. Thus, biglycan deficiency reduces vascular smooth muscle cell proliferation and migration, resulting in an attenuation of vascular injury. We hypothesize that the upregulation of biglycan by vascular injury actually contributes to the lesion development, rather than being a secondary outcome of the injury. Strategies to attenuate the upregulation of biglycan by vascular injury may have clinical benefits.