Over 190 million people worldwide have diabetes and vascular complications are the major causes of increased
mortality and morbidity in diabetic patients. Specifically, type 2 diabetes is associated with an increased rate of hypertension and restenosis.
While the underlying molecular mechanisms remain largely unknown, it is well documented that reactive oxygen species (ROS) is significantly
increased in the vascular wall in diabetes and the increased ROS plays important roles in various diabetic vascular complications. However, the
precise molecular mechanisms by which type 2 diabetes increases vascular ROS and the mechanisms by which the increased vascular ROS contribute to
the diabetes-associated hypertension and restenosis remain largely unknown.
iPLA2 (calcium independent phospholipase A2) is a member of the phospholipase A2 superfamily that is expressed in vascular smooth muscle and
exhibits diverse cellular functions. We have found that iPLA2 is activated/up-regulated in the vasculature of type 2 diabetic db/db mice and
high-fat diet-fed mice, and by high glucose in primary cultured vascular smooth muscle cells (VSMC). Moreover, inhibition of iPLA2 by pharmacological
inhibitor, or genetic deletion abolishes, whereas overexpression of iPLA2 exacerbates high glucose-induced NAD(P)H oxidase-mediated superoxide
production in cultured VSMCs. These data suggest that iPLA2 is required for high glucose-induced NAD(P)H oxidase-mediated ROS production in cultured
VSMCs and thus implicate an potentially important role of iPLA2 in the diabetes induced ROS increase in vascular wall. With a long-term goal of
identifying novel therapeutic target for type 2 diabetic vascular complications, the urrent research in my laboratory focuses on the molecular mechanisms
of type 2 diabetes-associated hypertension and restenosis.
Combinations of the state-of-the-art techniques with classical physiological and biochemical methods were used to pursue our goals. These include
radiotelemetry monitoring mouse blood pressure, smooth muscle specific transgenic and knockout mouse models, HPLC to detect superoxide, real-time PCR,
and adenoviral mediated gene transfer etc.
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