Anti‐atherosclerotic effects of vitamin E – myth or reality?

Abstract

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPHoxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.

Induction of reactive oxygen species from isolated rat glomeruli by protein kinase C activation and TNF-α stimulation, and effects of a phosphodiesterase inhibitor

“…It has a chromanic nucleus, with an aliphatic side chain which can protect lipid structures from peroxidation (Munteanu et al, 2004). In addition, it has also been reported that α-tocopherol inhibits NADPH oxidase by suppressing PKC-mediated phosphorylation and translocation of p47-phox (Cachia et al, 1998).…”

Present trends in vitamin E research

“…Intracellular players in signaling expected to be influenced by the interaction between these proteins and vitamin E are numerous (reviewed in [4][5][6][7]) and include kinases such as PKC, Akt/PKB, some members of MAPK family and cell cycle related kinases, and the recently proposed downstream components of the death domain and proteins of the endoplasmic reticulum stress signaling [8]. Tocotrienols have been reported to be ligands of the estrogen receptor b (ERb) [9] that could thus contribute some aspects of vitamin E signaling that will be further discussed later in the section dedicated to tocotrienols.…”

Antioxidantes dietéticos: controvérsias e perspectivas

“…em pessoas fumantes ou que consumam quantidade elevada de PUFAs 36 . A partir destes resultados contraditórios, estudos in vitro têm demonstrado que em doses elevadas o α-tocoferol pode agir como pró-oxidante, caso não haja concentrações equivalentes de outros antioxidantes para regenerar o radical α-tocoferila a α-tocoferol 25 .…”

“…A vitamina E atua em nível celular, inibindo a proliferação de células musculares lisas das artérias, a agregação plaquetária, a adesão de monócitos à parede do endotélio, a captação de LDL oxidada e a produção de citocinas. Estes mecanismos parecem estar relacionados com efeitos específicos do α-tocoferol na transdução de sinais e expressão gênica 25,37 .…”