engleski

Omega-3 Fatty Acids and the Membrane Transport System and Channels in Endothelium

Potential beneficial effects of dietary daily intake of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as α‐linolenic fatty acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) on vascular function, hemorrheological characteristic of the blood and and potential to improve physical performance as well as other cardiovascular parameters are currently intensively investigated. However, their molecular targets remain largely unknown and deserve attention. Research activities are mainly directed toward pulmonary circulation (due to potential effects in the treatment of pulmonary hypertension) and in macrocirculation (for possible antithrombotic and atherosclerotic effects) and microcirculation (such as coronary microcirculation, investigating molecular targets related to endothelial function). Recently, ion channels have been in the focus of interest as molecullar target of n-3 PUFAs effects. In studies on human entothelial cells, it has been shown that n-3 PUFAs metabolites are required for TRPV4 channel activity. This effect occur possible due to the membrane's eicosanoid's epoxide group location which increases membrane fluidity and influences the endothelial cell response by increasing TRPV4 channel activity. Other channels have also been modified by n-3 PUFAs. For example, DHA induced dose-dependent activation of the calcium-activated K+ (KCa) current in primary human PASMCs and endothelium-dependent relaxation of pulmonary arteries. The increased K2P 6.1-gene expression may represent a novel counter-regulatory mechanism in pulmonary hypertension. Furthermore, 17S-HDHA, an endothelium-derived DHA product via lipoxygenase, activates BK(Ca) channels in coronary arterial smooth muscle cells, leading to coronary vasodilation in coronary microvessels. Additionally, EPA modulated intracelullular Ca2' signaling in vascular smooth muscle cells, by blocking Ca2' current and inducing relaxation, directly or by their epoxygenases' metabolites. This is also mediated by activation of K' channels and EPA via upregulation of UCP-2 activates AMPKα1 resulting in increased eNOS phosphorylation and consequent improvement of endothelial function in vivo. In conclusion, n-3 PUFAs can significantly modify cellular function, as demonstrated in in vitro and animal models ; however, there is a paucity of data in human randomized controlled clinical studies which could confirm in vivo such effects.

n-3 PUFAs, EPA, DHA, microcirculation, potassium channels, calcium channels, pulmonary hypertension, coronary microcirulation

This work was supported by European Structural and Investment Funds, grant for the Croatian National Scientific Center of Excellence for Personalized Health Care, University Josip Juraj Strossmayer Osijek, #KK.01.1.1.01.0010.