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. 2007 May 1;8(4):526–536. doi: 10.1111/j.1582-4934.2004.tb00477.x

Expression of phospholipase D isozymes in scar and viable tissue in congestive heart failure due to myocardial infarction

Melissa R Dent 1, Tushi Singal 1, Naranjan S Dhalla 1, Paramjit S Tappia 2,✉
PMCID: PMC6740262  PMID: 15601581

Abstract

The phospholipase D (PLD) associated with the cardiac sarcolemmal (SL) membrane hydrolyses phosphatidylcholine to produce phosphatidic acid, an important phospholipid signaling molecule known to influence cardiac function. The present study was undertaken to examine PLD isozyme mRNA expression, protein contents and activities in congestive heart failure (CHF) subsequent to myocardial infarction (MI). MI was induced in rats by occlusion of the left anterior descending coronary artery. At 8 weeks after the surgical procedure, hemodynamic assessment revealed that these experimental rats were at a moderate stage of CHF. Semi‐quantitative reverse transcriptase‐polymerase chain reaction revealed that PLD1 and PLD2 mRNA amounts were unchanged in viable left ventricular (LV) tissue of the failing heart. Furthermore, this technique demonstrated the presence of PLD1 and PLD2 mRNA in the scar tissue. While SL PLD1 and PLD2 protein contents were elevated in the viable LV tissue of the failing heart, SL PLD1 activity was significantly decreased, whereas SL PLD2 activity was significantly increased. On the other hand, although PLD1 protein was undetectable, PLD2 protein and activity were detected in the scar tissue. Our findings suggest that differential changes in PLD isozymes may contribute to the pathophysiology of CHF and may also be involved in the processes of scar remodeling.

Keywords: congestive heart failure, myocardial infarction, cardiac sarcolemma, scar tissue, phospholipase D isozymes

References

  • 1. Panagia V., Ou C., Taira Y., Dai J., Dhalla N.S., Phospholipase D activity in subcellular membranes of rat ventricular myocardium, Biochim. Biophys. Acta., 1064: 242–250, 1991. [DOI] [PubMed] [Google Scholar]
  • 2. Ye H., Wolf R.A., Kurz T., Corr P.B., Phosphatidic acid increases in response to noradrenaline and endothelin‐1 in adult rabbit ventricular myocytes, Cardiovasc. Res., 28: 1828–1834, 1994. [DOI] [PubMed] [Google Scholar]
  • 3. Sadoshima J., Izumo S., Signal transduction pathways of angiotensin II‐induced c‐fos gene expression in cardiac myocytes in vitro. Roles of phospholipid‐derived second messengers, Circ. Res., 73: 424–438, 1993. [DOI] [PubMed] [Google Scholar]
  • 4. Xu Y‐J., Botsford M.W., Panagia V., Dhalla N.S., Responses of heart function and intracellular free Ca2+ to phosphatidic acid in diabetic rats, Can. J. Cardiol., 12: 1092–1098, 1996. [PubMed] [Google Scholar]
  • 5. Dhalla N.S., Xu Y‐J., Sheu S‐S., Tappia P.S., Panagia V., Phosphatidic acid: a potential signal transducer for cardiac hypertrophy, J. Mol. Cell. Cardiol., 29: 2865–2871, 1997. [DOI] [PubMed] [Google Scholar]
  • 6. Xu Y‐J., Panagia V., Shao Q., Wang X., Dhalla N.S., Phosphatidic acid increases intracellular free Ca2+and cardiac contractile force, Am. J. Physiol. 271: H651–H659, 1996. [DOI] [PubMed] [Google Scholar]
  • 7. Colley W.C., Sung T‐C., Roll R., Jenco J., Hammond S.M., Altshuller Y., Bar‐Sagi D., Morris A.J., Frohman M.A., Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization, Curr. Biol., 7: 191–201, 1997. [DOI] [PubMed] [Google Scholar]
  • 8. Frohman M.A., Morris A.J., Phospholipase D structure and function, Chem. Phys. Lipids, 98: 127–140, 1999. [DOI] [PubMed] [Google Scholar]
  • 9. Lee T.G., Park J.B., Lee S.D., Hong S., Kim J.H., Kim Y., Yi K.S., Bae S., Hannun Y.A., Obeid L.M., Suh S.G., Ryu S.H., Phorbol myristate acetate‐dependent association of protein kinase C α with phospholipase D1 in intact cells, Biochim. Biophys. Acta, 1347: 199–204, 1997. [DOI] [PubMed] [Google Scholar]
  • 10. Kim J.H., Lee S.D., Han J.M., Lee T.G., Kim Y., Park J.B., Lambeth J.D., Suh P.G., Ryu S.H., Activation of phospholipase D1 by direct interaction with ADP‐ribosylation factor 1 and Ra1A, FEBS Lett., 430: 231–235, 1998. [DOI] [PubMed] [Google Scholar]
  • 11. Yamazaki M., Zhang Y., Watanabe H., Yokozeki T., Ohno S., Kaibuchi K., Shibata H., Mukai H., Ono Y., Frohman M.A., Kanaho Y., Interaction of the small G protein RhoA with the C terminus of human phospholipase D1, J. Biol. Chem., 274: 6035–6038, 1999. [DOI] [PubMed] [Google Scholar]
  • 12. Hammond S.M., Jenco J.M., Nakashima S., Cadwallader K., Cook S., Nozawa Y., Frohman M.A., Morris A.J., Characterization of two alternately spliced forms of phospholipase D1: Activation of the purified enzymes by phosphatidylinositol 4,5‐ bisphosphate, ADP‐ribosylation factor, and Rho family monomeric GTP‐binding proteins and protein kinase C‐α, J. Biol. Chem., 272: 3860–3868, 1997. [DOI] [PubMed] [Google Scholar]
  • 13. Sciorra V.A., Rudge S.A., Prestwich G.D., Frohman M.A., Engebrecht J., Morris A.J., Identification of a phosphoinositide binding motif that mediates activation of mammalian and yeast phospholipase D isoenzymes, EMBO J., 18: 5911–5921, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Kim J.H., Kim Y., Lee S.D., Lopez I., Arnold R.S., Lambeth J.D., Suh P.G., Ryu S.H., Selective activation of phospholipase D2 by unsaturated fatty acids, FEBS Lett., 454: 42–46, 1999. [DOI] [PubMed] [Google Scholar]
  • 15. Dai J., Williams S.A., Ziegelhoffer A., Panagia V., Structure‐activity relationship of the effect of cis‐unsaturated fatty acids on heart sarcolemmal phospholipase D activity, Prostagland. Leuk. Essent. Fatty Acids, 52: 167–171, 1995. [DOI] [PubMed] [Google Scholar]
  • 16. Liu S‐Y., Tappia P.S., Dai J., Williams S.A., Panagia V., Phospholipase A2‐mediated activation of phospholipase D in rat heart sarcolemma, J. Mol. Cell. Cardiol., 30: 1203–1214, 1998. [DOI] [PubMed] [Google Scholar]
  • 17. Sarri E., Pardo R., Fensome‐Green A., Cockcroft S., Endogenous phospholipase D2 localizes to the plasma membrane of RBL‐2H3 mast cells and can be distinguished from ADP ribosylation factor‐stimulated phospholipase D1 activity by its specific sensitivity to oleic acid, Biochem. J., 369: 319–329, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Park J.B., Kim J.H., Kim K.Y., Ha S.H., Kim J.H., Yoo J.‐S., Du G., Frohman M.A., Suh P.‐G., Ryu S.H., Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by α‐actinin in an ADP‐ribosylation factor‐reversible manner, J. Biol. Chem., 275: 21295–21301, 2000. [DOI] [PubMed] [Google Scholar]
  • 19. Dhalla N.S., Dixon I.M.C., Beamish R.E., Biochemical basis of heart function and contractile failure, J. Appl. Cardiol., 6: 7–30, 1991. [Google Scholar]
  • 20. Tappia P.S., Yu C‐H., DiNardo P., Pasricha A.K., Dhalla N.S., Panagia V., Depressed responsiveness of phospholipase C isozymes to phosphatidic acid in congestive heart failure, J. Mol. Cell. Cardiol., 33: 431–440, 2001. [DOI] [PubMed] [Google Scholar]
  • 21. Yu C‐H., Panagia V., Tappia P.S., Liu S.‐Y., Takeda N., Dhalla N.S., Alterations of sarcolemmal phospholipase D and phosphatidate phosphohydrolase in congestive heart failure, Biochim. Biophys. Acta., 1584: 65–72, 2002. [DOI] [PubMed] [Google Scholar]
  • 22. Ju H., Zhao S., Tappia P.S., Panagia V., Dixon I.M.C., Expression of Gqα and PLC‐α in scar and border tissue in heart failure due to myocardial infarction, Circulation, 97: 892–898, 1998. [DOI] [PubMed] [Google Scholar]
  • 23. Tappia P.S., Liu S‐Y., Shatadal S., Takeda N., Dhalla N.S., Panagia V., Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril, Am. J. Physiol. 277: H40–H49, 1999. [DOI] [PubMed] [Google Scholar]
  • 24. McHowat J., Tappia P.S., Liu S‐Y., McCrory R., Panagia V., Redistribution and abnormal activity of phospholipase A2 in postinfarct congestive heart failure, Am. J. Physiol. 280: C573–C580, 2001. [DOI] [PubMed] [Google Scholar]
  • 25. Dent M.R., Dhalla N.S., Tappia P.S., Phospholipase C gene expression, protein content, and activities in cardiac hypertrophy and heart failure due to volume overload, Am. J. Physiol. 287: H719–H727, 2004. [DOI] [PubMed] [Google Scholar]
  • 26. Fahimi‐Vahid M., Gosau N., Michalek C., Han L., Jakobs K.H., Schmidt M., Roberts N., Avkiran M., Wieland T., Distinct signaling pathways mediate cardiomyocyte phospholipase D stimulation by endothelin‐1 and thrombin, J. Mol. Cell. Cardiol., 34: 441–453, 2002. [DOI] [PubMed] [Google Scholar]
  • 27. Goel D.P., Vecchini A., Panagia V., Pierce G.N., Altered cardiac Na+/H+ exchange in phospholipase D‐treated sarcolemmal vesicles, Am. J. Physiol. 279: H1179–H1184, 2000. [DOI] [PubMed] [Google Scholar]
  • 28. Philipson K.D., Nishimoto A.Y., Stimulation of Na+ ‐ Ca2+ exchange in cardiac sarcolemmal vesicles by phospholipase D, J. Biol. Chem., 259: 16–19, 1984. [PubMed] [Google Scholar]
  • 29. Langer G.A., Rich T.L., Phospholipase D produces increased contractile force in rabbit ventricle muscle, Circ. Res., 56: 146–149, 1985. [DOI] [PubMed] [Google Scholar]
  • 30. Knabb M.T., Rubio R., Berne R.M., Calcium‐dependent atrial slow action potentials generated with phosphatidic acid or phospholipase D, Pflügers Arch., 401: 435–437, 1984. [DOI] [PubMed] [Google Scholar]
  • 31. Dhalla N.S., Afzal N., Beamish R.E., Naimark B., Takeda N, Nagano M., Pathophysiology of cardiac dysfunction in congestive heart failure, Can. J. Physiol., 9: 873–887, 1993. [PubMed] [Google Scholar]
  • 32. Sandmann S., Min J.Y., Meissner A., Unger T., Effects of calcium channel antagonist mibefradil on haemodynamic parameters and myocardial Ca2+ ‐ handling in infarct‐induced heart failure in rats, Cardiovasc. Res., 44: 67–80, 1999. [DOI] [PubMed] [Google Scholar]
  • 33. Sjaastad I., Bentzen J.G., Semb, S.O. , Ilebekk A., Sejersted O.M., Reduced calcium tolerance in rat cardiomyocytes after myocardial infarction, Acta Physiol. Scand., 175: 261–269, 2002. [DOI] [PubMed] [Google Scholar]
  • 34. Moraru I.I., Popescu L.M., Maulik N., Liu X., Das D.K., Phospholipase D signaling in ischemic heart, Biochim. Biophys. Acta., 1139: 148–154, 1992. [DOI] [PubMed] [Google Scholar]
  • 35. Trifan O.C., Popescu L.M., Tosaki A., Cordis G., Das D.K., Ischemic preconditioning involves phospholipase D, Ann N Y Acad. Sci., 793: 485–488, 1996. [DOI] [PubMed] [Google Scholar]
  • 36. Tosaki A., Maulik N., Cordis G., Trifan O.C., Popescu L.M., Das D.K., Ischemic preconditioning triggers phospholipase D signaling in rat heart, Am. J. Physiol. 273: H1860–H1866, 1997. [DOI] [PubMed] [Google Scholar]
  • 37. Moraru I.I., Popescu L.M., Liu X., Engelman R.M., Das D.K., Role of phospholipase A2, C and D activation during myocardial ischemia and reperfusion, Ann. NY Acad. Sci., 723: 328–332, 1994. [PubMed] [Google Scholar]
  • 38. Kasai T., Ohguchi K., Nakashima S., Ito Y., Naganawa T., Kondo N., Nozawa Y., Increased activity of oleate‐dependent type phospholipase D during actinomycin D‐induced apoptosis in Jurkat T cells, J. Immunol., 161: 6469–6474, 1998. [PubMed] [Google Scholar]
  • 39. Yamakawa H., Banno Y., Nakashima S., Sawada M., Yamada J., Yoshimura S., Nishimura Y., Nozawa Y., Sakai N., Increased phospholipase D2 activity during hypoxia‐induced death of PC12 cells: its possible anti‐apoptotic role, Neuroreport., 11: 3647–3650, 2000. [DOI] [PubMed] [Google Scholar]
  • 40. Plevin R., Kellock N.A., Wakelam M.J., Wadsworth R., Regulation by hypoxia of endothelin‐1‐stimulated phospholipase D activity in sheep pulmonary artery cultured smooth muscle cells, Br. J. Pharmacol., 112: 311–315, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Popescu A.T., Vidulescu C., Stanciu C.L., Popescu B.O., Popescu L.M., Selective protection by phosphatidic acid against staurosporine‐induced neuronal apoptosis, J. Cell. Mol. Med., 6: 433–438, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Vidulescu C., Mironneau J., Mironneau C., Popescu L.M., Messenger molecules of the phospholipase signaling system have dual effects on vascular smooth muscle contraction, J. Cell. Mol. Med., 4: 196–206, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Vidulescu C., Mironneau J., Mironneau C., Popescu L.M., Phospholipase C and A2 trigger and sustain contraction, while phospholipase D intermediates relaxation in noradrenaline‐stimulated portal vein smooth muscle, J. Med. Biochem., 4: 22–31, 2000. [Google Scholar]
  • 44. Pfeffer M.A., Braunwald E., Ventricular remodeling after myocardial infarction: experimental observations and clinical implications, Circulation, 81: 1161–1172, 1990. [DOI] [PubMed] [Google Scholar]
  • 45. Weber K.T., Sun Y., Katwa L.C., Wound healing following myocardial infarction, Clin. Cardiol., 19: 447–455, 1996. [DOI] [PubMed] [Google Scholar]
  • 46. Fishbein M.C., Maclean D., Maroko P.R., Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution, Am. J. Pathol., 90: 57–70, 1978. [PMC free article] [PubMed] [Google Scholar]
  • 47. Hao J., Wang B., Jones S.C., Jassal D.S., Dixon I.M.C., Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro, Am. J. Physiol. 279: H3020–H3030, 2000. [DOI] [PubMed] [Google Scholar]
  • 48. Wang B., Hao J., Jones S.C., Yee M.‐Y., Roth J., Dixon I.M.C., Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart, Am. J. Physiol. 282: H1685–H1696, 2002. [DOI] [PubMed] [Google Scholar]
  • 49. Xu Y‐J., Chapman D., Dixon I.M.C., Sethi R., Guo X., Dhalla N.S., Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation, J. Cell. Mol. Med., 8: 85–92, 2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. Yamamoto K., Takahashi Y., Mano T., Sakata Y., Nishikawa N., Yoshida J., Oishi Y., Hori M., Miwa T., Inoue S., Masuyama T., N‐methylethanolamine attenuates cardiac fibrosis and improves diastolic function: inhibition of phospholipase D as a possible mechanism, Eur. Heart J., 25: 1221–9, 2004. [DOI] [PubMed] [Google Scholar]
  • 51. Hodgkin M.N., Pettitt T.R., Martin A., Michell R.H., Pemberton A.J., Wakelam M.J.O., Diacylglycerols and phosphatidates: which molecular species are intracellular messengers Trends Biochem. Sci. 23: 200–204, 1998. [DOI] [PubMed] [Google Scholar]

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