title: CD36 protein influences myocardial Ca2+ homeostasis and phospholipid metabolism: conduction anomalies in CD36-deficient mice during fasting.
abstract: Sarcolemmal CD36 facilitates myocardial fatty acid (FA) uptake, which is markedly reduced in CD36-deficient rodents and humans. CD36 also mediates signal transduction events involving a number of cellular pathways. In taste cells and macrophages, CD36 signaling was recently shown to regulate store-responsive Ca(2+) flux and activation of Ca(2+)-dependent phospholipases A(2) that cycle polyunsaturated FA into phospholipids. It is unknown whether CD36 deficiency influences myocardial Ca(2+) handling and phospholipid metabolism, which could compromise the heart, typically during stresses. Myocardial function was examined in fed or fasted (18-22 h) CD36(-/-) and WT mice. Echocardiography and telemetry identified conduction anomalies that were associated with the incidence of sudden death in fasted CD36(-/-) mice. No anomalies or death occurred in WT mice during fasting. Optical imaging of perfused hearts from fasted CD36(-/-) mice documented prolongation of Ca(2+) transients. Consistent with this, knockdown of CD36 in cardiomyocytes delayed clearance of cytosolic Ca(2+). Hearts of CD36(-/-) mice (fed or fasted) had 3-fold higher SERCA2a and 40% lower phospholamban levels. Phospholamban phosphorylation by protein kinase A (PKA) was enhanced after fasting reflecting increased PKA activity and cAMP levels in CD36(-/-) hearts. Abnormal Ca(2+) homeostasis in the CD36(-/-) myocardium associated with increased lysophospholipid content and a higher proportion of 22:6 FA in phospholipids suggests altered phospholipase A(2) activity and changes in membrane dynamics. The data support the role of CD36 in coordinating Ca(2+) homeostasis and lipid metabolism and the importance of this role during myocardial adaptation to fasting. Potential relevance of the findings to CD36-deficient humans would need to be determined.
authors.affiliation: Center for Human Nutrition, Washington University, St. Louis, Missouri 63110, USA.
authors.forename: Terri A
authors.initials: TA
authors.lastname: Pietka
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Sulkin
authors.forename: Ondrej
authors.initials: O
authors.lastname: Kuda
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Dequan
authors.initials: D
authors.lastname: Zhou
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Yamada
authors.forename: Kui
authors.initials: K
authors.lastname: Yang
authors.forename: Xiong
authors.initials: X
authors.lastname: Su
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gross
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Nerbonne
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
mesh_terms: D000821:Animal Feed; D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004562:Electrocardiography / Q000379:methods; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D000242:Cyclic AMP; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium