Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat.
Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function),and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy.
College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. bakinwumi@sbrc.ca.|Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. bakinwumi@sbrc.ca.
Bolanle C
BC
Akinwumi
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. praj@sbrc.ca.|Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. praj@sbrc.ca.|Agriculture and Agri-Food Canada, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. praj@sbrc.ca.
Pema
P
Raj
College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. dlee@sbrc.ca.|Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. dlee@sbrc.ca.
Danielle I
DI
Lee
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. cacosta@sbrc.ca.|Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. cacosta@sbrc.ca.
Crystal
C
Acosta
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. lyu@sbrc.ca.|Agriculture and Agri-Food Canada, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. lyu@sbrc.ca.
Liping
L
Yu
Sami Labs Ltd., Peenya Industrial Area, Bangalore 560058, India. samuelmanoharan@samilabs.com.
Samuel M
SM
Thomas
Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. kalyanam@sabinsa.com.
Kalyanam
K
Nagabhushanam
Sami Labs Ltd., Peenya Industrial Area, Bangalore 560058, India. kalyanam@sabinsa.com.|Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. kalyanam@sabinsa.com.
Muhammed
M
Majeed
College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. ndavies@ualberta.ca.|Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 2-35, Medical Sciences Building, Edmonton, AL T6G 2H7, Canada. ndavies@ualberta.ca.
Neal M
NM
Davies
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. tnetticadan@sbrc.ca.|Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. tnetticadan@sbrc.ca.|Agriculture and Agri-Food Canada, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. tnetticadan@sbrc.ca.
Thomas
T
Netticadan
College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. handerson@sbrc.ca.|Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada. handerson@sbrc.ca.|Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. handerson@sbrc.ca.
Hope D
HD
Anderson
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006334:Heart Function Tests; D020935:MAP Kinase Signaling System / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology
C476734:2,3',5',6-tetrahydroxy-trans-stilbene; D059808:Polyphenols; D013267:Stilbenes; C107773:pterostilbene; D000077185:Resveratrol
heart failure; hypertension; polyphenol; resveratrol; stilbenoid