Dietary Polyunsaturated Fatty Acids (PUFAs) and Cardiomyocyte Function
Jos M.J. Lamers, Dick H.W. Dekkers, Henriette de Jonge, Yvonne E.G. Eskildsen-Helmond, Han A.A. van Heugten.
Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine & Health Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands
The fatty acyl composition of cardiac sarcolemma, like the plasmamembranes of other cell types, can be markedly altered by dietary means especially by changing the degree of polyunsaturation. For this reason it is important to understand the consequences in terms of cardiac membrane phospholipid dynamics and function. Firstly, the relative nature (n-3 versus n-6 type) and quantity of PUFAs in cardiac membranes regulate the rate and extent of lipidperoxidation. We could, however, demonstrate that in spite of the increased susceptibility of cardiac sarcolemma to free radical generated peroxidation in fish oil compared to lard fed pigs, the recovery of left ventricular function was similar following multiple short-term periods of coronary occlusion. Secondly, membrane phospholipids and the incorporated PUFAs contain 'information' in addition their structural role. The 'information' can be released by action of several types of phospholipases (e.g. phospholipase A2, C-b and D). We could show that increased incorporation of n-3 or n-6 PUFAs results in reduction of a1-adrenergic agonist mediated Gq-phospholipase C-b signaling in cultured rat cardiomyocytes. These data were consistent with the earlier observed in vivo effects of dietary n-3 PUFA on the cardiac positive inotropic response to a1-adrenergic agonists. Exposure for 24 hrs of cultured cardiomyocytes to 20:5n-3 (already detectable at 50 mM) but not to 18:2n-6 or 18:0/18:1n-9, induced cellular accumulation of glycero-P-inositol which likely is caused by an increase in phospholipase A mediated phospholipid turnover. On the other hand, cross-talk between phospholipase C-b and D via protein kinase C could be demonstrated to occur in the cardiomyocyte preparation during endothelin-1 and a1-adrenergic agonist stimulation. The latter signalling processes have definitely been shown to play a central role in the cardiac hypertrophic response. Another remarkable finding in the experiments on cross-talk between phospholipases was that during the stimulation by agonist the 1,2-diacylglycerol level remained relatively constant despite occurrence of a rapid translocation/activation of protein kinase C isoform e. It indicates that the PUFA composition of 1,2-diacyl glycerol rather than its total concentration determines the activation of protein kinase C. In conclusion, PUFAs of cardiac membrane phospholipids have not only a structural role but also determine their susceptibility to lipid peroxidation and their functions in agonist-mediated transmembrane signalling (supported by grants from the Dutch Organization for Scientific Research, NWO).