Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts

Insight with genomics

Somak Das, Subhendu Mukherjee, I. Lekli, Narasimman Gurusamy, Jayeeta Bardhan, Utpal Raychoudhury, Runu Chakravarty, Sandip Banerji, Anne A. Knowlton, Dipak K. Das

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Most clinical trials with vitamin E could not lower cholesterol and thus, have been deemed unsuccessful. Recently, tocotrienols, isomers of vitamin E have been found to lower LDL levels. To explore if tocotrienols could be the drug target for vitamin E, rabbits were kept on cholesterol diet for 60 days supplemented with tocotrienol-α, tocotrienol-δ, and tocotrienol-γ for the last 30 days. The serum cholesterol levels (in mmol/l) were 24.4 (tocotrienol-α), 34.9 (tocotrienol-δ), 19.8 (tocotrienol-γ) vs. 39.7 (control). Left ventricular function including aortic flow and developed pressure exhibited significantly improved recovery with tocotrienol-γ and -α, but not with tocotrienol-δ. The myocardial infarct size showed a similar pattern: 33% (tocotrienol-α), 23% (tocotrienol-γ), and 47% (tocotrienol-δ). To examine the molecular mechanisms of cardioprotective effects, gene expression profile was determined using Atlas 1.2/1.2II followed by determination of gene profiles using PedQuest 8.3 software. Based on genomic profiles, the following cholesterol-related proteins were examined: FABP, TGF-β (cholesterol suppresses TGF-β), ET-1 (increased by hypercholesterolemia), SPOT 14 (linked with hypercholesterolemia), and matrix metalloproteinase (MMP) 2 and MMP9 (cholesterol regulates MMP2 and MMP9 expression) in the heart. Consistent with the cardioprotective effects of tocotrienol-α and -γ, these two isomers reduced ET-1, decreased MMP2 and MM9, increased TGF-β and reduced SPOT 14, while tocotrienol-δ had no effects. The results of the present study demonstrate that the two isomers of tocotrienols, α and γ, render the hypercholesterolemic hearts resistant to ischemic reperfusion injury by lowering several hypercholesterolemic proteins including MMP2, MMP9, ET-1, and SPOT 14 and upregulating TGF-β.

Original languageEnglish
Pages (from-to)35-45
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume360
Issue number1-2
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Tocotrienols
Genomics
Ischemia
Cholesterol
Vitamin E
Isomers
Hypercholesterolemia

Keywords

  • Gene expression
  • Genomics
  • Heart
  • Hypercholesterolemia
  • Tocotrienols

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts : Insight with genomics. / Das, Somak; Mukherjee, Subhendu; Lekli, I.; Gurusamy, Narasimman; Bardhan, Jayeeta; Raychoudhury, Utpal; Chakravarty, Runu; Banerji, Sandip; Knowlton, Anne A.; Das, Dipak K.

In: Molecular and Cellular Biochemistry, Vol. 360, No. 1-2, 01.2012, p. 35-45.

Research output: Contribution to journalArticle

Das, S, Mukherjee, S, Lekli, I, Gurusamy, N, Bardhan, J, Raychoudhury, U, Chakravarty, R, Banerji, S, Knowlton, AA & Das, DK 2012, 'Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: Insight with genomics', Molecular and Cellular Biochemistry, vol. 360, no. 1-2, pp. 35-45. https://doi.org/10.1007/s11010-011-1041-9
Das, Somak ; Mukherjee, Subhendu ; Lekli, I. ; Gurusamy, Narasimman ; Bardhan, Jayeeta ; Raychoudhury, Utpal ; Chakravarty, Runu ; Banerji, Sandip ; Knowlton, Anne A. ; Das, Dipak K. / Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts : Insight with genomics. In: Molecular and Cellular Biochemistry. 2012 ; Vol. 360, No. 1-2. pp. 35-45.
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