title: Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension.
abstract: OBJECTIVE
  Alterations in intracellular Ca2+ concentration ([Ca2+]i) underlie the pathogenesis of various cardiovascular diseases. Caveolin-1 (Cav-1) is the primary functional protein associated with caveolae, which are invaginations in the plasma membrane, and is a regulator of [Ca2+]i signaling. Caveolae and Cav-1 increase the activity of store-operated Ca2+ channels (SOCC) in rat pulmonary arterial smooth muscle cells (PASMCs), and these enhancing effects were more pronounced in rats with pulmonary hypertension (PH). Classical transient receptor potential (TRPC) proteins are highly expressed in vascular smooth muscle cells, and these proteins form functional receptor-operated Ca2+ channels (ROCC) and SOCC in PASMCs. Previous studies suggested that functional and structural changes in aortas might occur during the pathological process of PH. Our data demonstrated that Cav-1 and TRPC were also abundant in the aorta smooth muscle cells (AoSMCs) of PH rats. However, previous PH research primarily focused on Ca2+ channels in pulmonary arteries, but not functional changes in Ca2+ channels in aortas. The contribution of Cav-1 of AoSMCs to alterations of Ca2+ signaling in aortic functions during the pathological process of PH has not been fully characterized. Therefore, this study investigated alterations in Cav-1 expression and the relationship of these changes to Ca2+ channels in AoSMCs of PH rats.
  
  
  METHODS
  The present study examined physiological caveolae and Cav-1 expression and characterized the function of altered Cav-1 expression in rat aortas with PH.
  
  
  RESULTS
  The appearance of caveolae with Cav-1 expression increased significantly in the aortas of rats with PH, but TRPC1 and TRPC6 expression was not altered. In vitro experiments demonstrated that caveolae contributed to phenylephrine, endothelin-1, and 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced aortic vasoreactivity, but KCl and cyclopiazonic acid had no effect, which suggests the vital ability of Cav-1 to regulate ROCC activity. The introduction of Cav-1 scaffolding domain peptide enhanced OAG-induced ROCC function in primary AoSMCs.
  
  
  CONCLUSIONS
  Cav-1 is specifically associated with ROCC in aortas and plays a vital role in altering vasoreactivity, which affects cardiovascular diseases pathology. Caveolae and Cav-1 up-regulation may affect the function of ROCC in rat models of PH.
authors.affiliation: Department of Physiology &amp; Pathophysiology and Laboratory of Cardiovascular Sciences, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, (People's Republic of China).
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Mu
authors.forename: Da-Cen
authors.initials: DC
authors.lastname: Lin
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Yan
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Jiao
authors.forename: Long-Xin
authors.initials: LX
authors.lastname: Gui
authors.forename: Mo-Jun
authors.initials: MJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; D011956:Receptors, Cell Surface; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D014662:Vasoconstrictor Agents; C096351:transient receptor potential cation channel, subfamily C, member 1; D010656:Phenylephrine; D002118:Calcium