Phospholamban Is Present in Endothelial Cells and Modulates Endothelium-Dependent Relaxation: Evidence From Phospholamban Gene-Ablated Mice

• Published in: Circulation research 1999-02, Vol.84 (3), p.360-364
• Main Authors: Sutliff, Roy L, Hoying, James B, Kadambi, Vivek J, Kranias, Evangelia G, Paul, Richard J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood vessels and receptors; Calcium - metabolism; Calcium-Binding Proteins - analysis; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - physiology; Cells, Cultured; Colforsin - pharmacology; Endothelium, Vascular - chemistry; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Mice; Mice, Knockout; Nitroprusside - pharmacology; Vasodilation - drug effects; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.84.3.360

Vascular endothelial cells regulate vascular smooth muscle tone through Ca production and release of vasoactive molecules. Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca]i and contractility in these muscles. In the present study, we report the existence of PLB in the vascular endothelium, a nonmuscle tissue, and provide functional data on PLB regulation of vascular contractility through its actions in the endothelium. Endothelium-dependent relaxation to acetylcholine was attenuated in aorta of PLB-deficient (PLB-KO) mice compared with wild-type (WT) controls. This effect was not due to actions of nitric oxide on the smooth muscle, because sodium nitroprusside-mediated relaxation in either denuded or endothelium-intact aortas was unaffected by PLB ablation. Relative to denuded vessels, relaxation to forskolin was enhanced in WT endothelium-intact aortas. The endothelium-dependent component of this relaxation was attenuated in PLB-KO aortas. To investigate whether these changes were due to PLB, WT mouse aorta endothelial cells were isolated. Both reverse transcriptase-polymerase chain reaction and Western blot analyses revealed the presence of PLB in endothelial cells, which were shown to be >98% pure by diI-acetylated LDL uptake and nuclear counterstaining. These data indicate that PLB is present and modulates vascular function as a result of its actions in endothelial cells. The presence of PLB in endothelial cells opens new fields for investigation of Ca regulatory pathways in nonmuscle cells and for modulation of endothelial-vascular interactions. (Circ Res. 1999;84:360-364.)