title: Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia.
abstract: BACKGROUND
  Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia.
  
  
  RESULTS
  Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (P<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (P=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (P=0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine (P=0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment (P=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine (P=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF (P=0.002), peNOS (ser1177) (P=0.04), NFkB (P=0.004), and pAkt (thr308) (P=0.001).
  
  
  CONCLUSIONS
  Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Robert M
authors.initials: RM
authors.lastname: Osipov
authors.forename: Reza
authors.initials: R
authors.lastname: Nezafat
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Richard T
authors.initials: RT
authors.lastname: Clements
authors.forename: Cesario
authors.initials: C
authors.lastname: Bianchi
authors.forename: Munir
authors.initials: M
authors.lastname: Boodhwani
authors.forename: Michael A
authors.initials: MA
authors.lastname: Coady
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Laham
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002196:Capillaries / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010477:Perfusion; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D000077185:Resveratrol