Type 2 diabetes is associated with a markedly increased risk for atherosclerotic coronary
arteries and cerebrovascular diseases. The major cause of death in diabetic patients is
cardiovascular disease in the world including Taiwan. Atherosclerosis is a progressive
disease characterized by the response of the vessel wall to chronic, multifactorial injury,
which leads ultimately to the formation of atheromatous or fibrous plaques. Endothelial
dysfunction is thought to be the initial stage of atherosclerosis. Endothelial dysfunction
leads to impaired control of vascular tone, a decreased in the release of anti-inflammatory
factors and reduced availability of nitric oxide. Endothelial dysfunction portends diabetic
vasculopathy. The loss of intact endothelial integrity and function sets in motion a cascade
of serial events that lead to atherosclerosis and cardiovascular complications.
The standard extracts of G. biloba leaves [G. biloba extract (GBE)] are now demonstrated the
cardiovascular, cerebrovascular and neuroprotective effects. The mixture of biologically
active ingredients in GBE accounts for the pleiotropic effects, including antioxidant
effects, inhibition of platelet aggregation and thromboxane B2 production, vasodilation and
modulation of cholesterol metabolism. Clinically, GBE was widely used in management of
vertigo、dementia and improving peripheral circulation. In our previous study, ginkgo biloba
extract inhibits tumor necrosis factor-alpha-induced reactive oxygen species generation,
transcription factor activation, and cell adhesion molecule expression in human aortic
endothelial cells. In addition, the similar benefit of prevention atherosclerosis was also
found in animal study.
Heme oxygenase-1 (HO-1) is a factor associated with higher risk of developing some vascular
disease and also a rate-limiting enzyme in heme degradation, leading to the generation of
free iron, biliverdin, and carbon monoxide (CO). CO exerts potent antiproliferative and
anti-inflammatory effects in the vascular walls, thereby influencing neointimal formation
after vascular injury. In addition, biliverdin is subsequently metabolized to bilirubin by
the enzyme biliverdin reductase. Therefore, induction of HO-1 elicits potent
anti-inflammatory, antiproliferative, antithrombotic, and antioxidant effects in the
circulation via the generation of CO and bilirubin. Interestingly, recent study found that a
long guanidine thymidine dinucleotide repeat [(GT) n≧ 30] in the HO-1 promotor, which is
linked to impaired inducibility, is associated with a higher frequency of vascular access
failure.
In the present study, we will investigate the effect of GBE on recovering endothelial
dysfunction and inflammation in diabetic patients with stable coronary artery disease. In
particularly, we intend to determine whether the GBE modulates the HO-1 expression and
investigate whose genotyping including some candidate gene about atherosclerosis and
hypertension will have most therapeutic effect of GBE.
