Key Findings
Angiogenesis is a complex process that requires growth factors such as vascular endothelial growth factor (VEGF) and the angiopoietin (Ang) systems that directly or indirectly affect the endothelial cells and produce proliferation and differentiation. The objective of the present study was to determine the angiogenic property of SDG. The effects of SDG on protein expression profiles of the VEGF-Ang system was studied using human coronary arteriolar endothelial cells (HCAEC) and rat myocardial ischemic models. The study showed that SDG is a potent angiogenic compound that has significant potential to be used as a clinical drug during myocardial ischemia. Some patients do not receive complete revascularization because of severe atherosclerotic lesions or total arterial occlusion. These patients suffer from effort angina pectoris and LV dysfunction. Therefore, neovascularization with SDG could benefit patients with coronary artery disease without going through PTCI and CABG interventions. Thus SDG, apart from reducing cholesterol levels, also induces angiogenesis-mediated cardioprotection by increasing neovascularization in the peri-infarct zone, leading to less ventricular remodeling.
ABSTRACT
Therapeutic angiogenesis represents a novel approach for the prevention and treatment of ischemic heart disease. This study examined a novel method of stimulating myocardial angiogenesis using secoisolariciresinol diglucoside (SDG), a plant lignan isolated from flaxseed. SDG has been shown to decrease serum cholesterol and reduce the extent of atherosclerosis. In the present study, the angiogenic properties of SDG were investigated in three different models. First, in the in vitro model, human coronary arteriolar endothelial cells (HCAEC) treated with SDG (50 and 100 microM) showed a significant increase in tubular morphogenesis compared with control. Western blot analysis indicated an increased expression of vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor (KDR), Flt-1, angiopoietin-1 (Ang-1), Tie-1, and phosphorylated endothelial nitric oxide synthase (p-eNOS) in the SDG-treated cells. Second, in the ex vivo ischemia/reperfusion model, SDG-treated rats (20 mg/kg b.wt./day for 2 weeks orally) showed an increased level of aortic flow and functional recovery after 2 h of reperfusion following 30 min of ischemia compared with the control group [dP/dt (mm Hg/s) of 2110 +/- 35 versus 1752 +/- 62]. SDG reduced infarct size compared with the control group by 32% (38 versus 26%) and also decreased cardiomyocyte apoptosis. Increased protein expression of VEGF, Ang-1, and p-eNOS was also observed in the SDG-treated group. Third, in the in vivo myocardial infarction model, SDG increased capillary density and myocardial function as evidenced by increased fractional shortening and ejection fraction. In conclusion, these results suggest that SDG has potent angiogenic and antiapoptotic properties that may contribute to its cardioprotective effect in ischemic models.