title: Secoisolariciresinol diglucoside: 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 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.
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030-1110, USA.
authors.forename: Suresh Varma
authors.initials: SV
authors.lastname: Penumathsa
authors.forename: Srikanth
authors.initials: S
authors.lastname: Koneru
authors.forename: Mahesh
authors.initials: M
authors.lastname: Thirunavukkarasu
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhan
authors.forename: Kailash
authors.initials: K
authors.lastname: Prasad
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Maulik
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002072:Butylene Glycols / Q000494:pharmacology*; D002478:Cells, Cultured; D004452:Echocardiography; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009024:Morphogenesis / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002072:Butylene Glycols; D005960:Glucosides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C090142:secoisolariciresinol diglucoside