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Published on: May 15, 2011

Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics

Somak Das1, Subhendu Mukherjee, Istvan Lekli

  • 1Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.

Molecular and Cellular Biochemistry
|September 16, 2011
PubMed

Insights

Tocotrienols, vitamin E isomers, show promise in protecting hearts from cholesterol damage. Tocotrienol-gamma and -alpha significantly lowered cholesterol and improved heart function in rabbits, unlike tocotrienol-delta.

Area of Science:

  • Cardiovascular Research
  • Nutritional Biochemistry
  • Molecular Medicine

Background:

  • Vitamin E clinical trials often fail to lower cholesterol.
  • Tocotrienols, isomers of vitamin E, have demonstrated LDL-lowering capabilities.
  • Hypercholesterolemia significantly impacts cardiovascular health and cardiac function.

Purpose of the Study:

  • To investigate the potential of tocotrienols as a therapeutic target for vitamin E in managing hypercholesterolemia.
  • To evaluate the cardioprotective effects of different tocotrienol isomers (alpha, gamma, delta) in a rabbit model of hypercholesterolemia.
  • To elucidate the molecular mechanisms underlying the cardioprotective effects of tocotrienols.

Main Methods:

  • Rabbits were fed a cholesterol-rich diet for 60 days, with tocotrienol supplementation during the final 30 days.
  • Serum cholesterol levels, left ventricular function (aortic flow, developed pressure), and myocardial infarct size were assessed.
  • Gene expression profiling was performed to analyze molecular mechanisms, focusing on cholesterol-related proteins (FABP, TGF-β, ET-1, SPOT 14, MMP2, MMP9).

Main Results:

  • Tocotrienol-gamma and -alpha significantly reduced serum cholesterol levels compared to the control group.
  • Left ventricular function and recovery were significantly improved by tocotrienol-gamma and -alpha.
  • Tocotrienol-gamma and -alpha reduced myocardial infarct size and modulated key proteins (ET-1, MMP2, MMP9, TGF-β, SPOT 14) associated with hypercholesterolemia and cardiac protection.
  • Tocotrienol-delta did not show significant cardioprotective effects or impact cholesterol levels.

Conclusions:

  • Tocotrienol-alpha and -gamma isomers demonstrate significant cardioprotective effects against ischemic reperfusion injury in hypercholesterolemic hearts.
  • These protective effects are mediated by the reduction of hypercholesterolemia-related proteins (MMP2, MMP9, ET-1, SPOT 14) and the upregulation of TGF-β.
  • Tocotrienols, specifically alpha and gamma isomers, represent a promising therapeutic strategy for managing cardiovascular complications associated with hypercholesterolemia.

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