Received for publication September 21, 2006.
Revised November 20, 2006.
Accepted for publication November 21, 2006.

SECOISOLARICIRESINOL DIGLUCOSIDE (SDG): RELEVANCE TO ANGIOGENESIS AND CARDIOPROTECTION AGAINST ISCHEMIA- REPERFUSION INJURY

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 flax seed. SDG has been shown to lower serum cholesterol and reduce the extent of atherosclerosis. In the present study, the angiogenic properties of SDG were investigated in three different models: 1) In vitro model, human coronary arteriolar endothelial cells (HCAEC) treated with SDG (50 & 100 µM) showed a significant increase in tubulogenesis compared to control. Western blot indicated an increased expression of VEGF, KDR, Flt-1, angiopoietin-1 (Ang-1), Tie-1 and phosphorylated eNOS (p-eNOS) in the SDG-treated cells 2) In ex vivo ischemia/reperfusion (I/R) model, SDG-treated rats (20 mg/kg b wt/day for 2 weeks orally) showed an increased level of aortic flow & functional recovery after 2 hr of reperfusion following 30 min of ischemia compared to the control group [dp/dt (mm Hg/sec) of 2110 ± 35 vs 1752 ± 62]. SDG reduced infarct size compared to the control group by 32% (38% vs 26%) and also decreased cardiomyocyte apoptosis. Increased protein expression of VEGF, Ang-1 and p-eNOS was also observed in the SDG-treated group 3) In in vivo myocardial infarction (MI) model, SDG increased capillary density and myocardial function as evidenced by increased fractional shortening and ejection fraction, assessed by echocardiogram. In conclusion, these results suggest that SDG has potent angiogenic and anti-apoptotic properties that may contribute to its cardioprotective effect in ischemic models.

Key words: Angiogenesis, Echocardiogram, VEGF, heart disease, infarct size, secoisolariciresinol diglucoside

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