Genomics unveils how tocotrienols alpha and gamma support heart health

Clinical trials focused on vitamin E were not successful to lower cholesterol. Das et al 2012 assessed the LDL reducing  role of isomers of vitamin E, the tocotrienols. Rabbits were submitted to cholesterol-rich diet supplemented with tocotrienols. [1]

The authors report that left ventricular function including aortic flow, the developed pressure, and the myocardial infarct size exhibited significantly improved recovery with tocotrienol-γ and -α, but not with tocotrienol-δ.

Genomics of improved heart conditions by tocotrienols
The authors explain that tocotrienol-γ and -α lower hypercholesterolemic proteins, such as the matrix metalloproteinase MMP2, MMP9(cholesterol regulates MMP2 and MMP9 expression), ET-1 which is increased by hypocholesterolemia, and SPOT 14 which is linked with hypercholesterolemia.  The cholesterol suppressing TGF-β was upregulated. Tocotrienol-δ had no effect.

Cardioprotection of red palmoil tocotrienols [2]
The tocotrienol-rich fraction (TRF) from red palm oil are being suggested by Das et al.2008 as  cardioprotective. Tocotrienol were also found to act neuroprotective against stroke. TRF of palm oil consists of three isoforms of tocotrienols (α, γ, and δ) as well as α-tocopherol.
The optimal concentration for TRF was determined by the authors being  3.5% TRF and 0.3 mg/kg body wt of tocotrienol given to rats for 4 weeks.

TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The gamma-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the alpha- and delta-isoforms.

The cardioprotection of tocotrienol isoforms were assessed by controlling their abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Tocotrienol isoforms generated a survival signal by reducing c-Src and increasing the phosphorylation of Akt.

Proteasomes are very large protein complexes located in the nucleus and the cytoplasm. They  degrade unneeded or damaged proteins. of particular proteins and degrade misfolded proteins by  proteolysis  C-src tyrosine kinase, also known as CSK, is a human protein and gene. It includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. This protein specifically phosphorylates Tyr-504 residue. [3]

[1] Das S, Mukherjee S, Lekli I, Gurusamy N, Bardhan J, Raychoudhury U, Chakravarty R, Banerji S, Knowlton AA, Das DK: Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics. Mol Cell Biochem. 2012 Jan;360(1-2):35-45.
http://www.ncbi.nlm.nih.gov/pubmed/21918828

[2] Das S, Lekli I, Das M, Szabo G, Varadi J, Juhasz B, Bak I, Nesaretam K, Tosaki A, Powell SR, Das DK: Cardioprotection with palm oil tocotrienols: comparision of different isomers. Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H970-8.
http://ajpheart.physiology.org/content/294/2/H970.long

[3] Proteasome. Wikipedia
http://en.wikipedia.org/wiki/Proteasome