title: Effects of chronic portal hypertension on small heat-shock proteins in mesenteric arteries.
abstract: Previous studies have shown that impaired vasoconstrictor function in chronic portal hypertension is mediated via cAMP-dependent events. Recent data have implicated two small heat-shock proteins (HSP), namely HSP20 and HSP27, in the regulation of vascular tone. Phosphorylation of HSP20 is associated with vasorelaxation, whereas phosphorylation of HSP27 is associated with vasoconstriction. We hypothesized that alterations in the expression and/or phosphorylation of small HSPs may play a role in impaired vasoconstriction in portal hypertension. A rat model of prehepatic chronic portal hypertension was used. Studies were conducted in small mesenteric arteries isolated from normal and portal hypertensive rats. Protein levels of HSP20 and HSP27 were detected by Western blot analysis. Protein phosphorylation was analyzed by isoelectric focusing. HSP20 mRNA expression was determined by RT-PCR. To examine the role of cAMP in the regulation of small HSP phosphorylation and expression, we treated both normal and portal hypertensive vessels with a PKA inhibitor Rp-cAMPS. We found both an increased HSP20 phosphorylation and a decreased HPS20 protein level in portal hypertension, both of which were restored to normal by PKA inhibition. However, PKA did not change HSP20 mRNA expression. We conclude that decreased HSP20 protein level is mediated by cAMP-dependent pathway and that impaired vasoconstrictor function in portal hypertension may be partially explained by decreased expression of HSP20. We also suggest that the phosphorylation of HSP20 by PKA may alter HSP20 turnover.
authors.affiliation: Dean, Graduate School and Professor of Pharmacology, Physiology & Therapeutics, Univ. of North Dakota, Grand Forks, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Kristin
authors.initials: K
authors.lastname: Pavlish
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Benoit
mesh_terms: D000818:Animals; D002908:Chronic Disease; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D050886:HSP20 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006975:Hypertension, Portal / Q000378:metabolism* / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology; D014661:Vasoconstriction
chemical_list: D050886:HSP20 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D013873:Thionucleotides; C087458:Hspb6 protein, rat; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases