title: HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice.
abstract: BACKGROUND
  CryAB (HspB5) and HspB2, two small heat shock genes located adjacently in the vertebrate genome, are hypothesized to play distinct roles. Mice lacking both cryab and hspb2 (DKO) are viable and exhibit adult-onset degeneration of skeletal muscle but confounding results from independent groups were reported for cardiac responses to different stressful conditions (i.e., ischemia/reperfusion or pressure overload). To determine the specific requirements of HSPB2 in heart, we generated cardiac-specific HSPB2 deficient (HSPB2cKO) mice and examined their cardiac function under basal conditions and following cardiac pressure overload.
  
  
  RESULTS
  Transverse aortic constriction (TAC) or sham surgery was performed in HSPB2cKO mice and their littermates (HSPB2wt mice). Eight weeks after TAC, we found that expression of several small HSPs (HSPB2, 5, 6) was not markedly modified in HSPB2wt mice. Both cardiac function and the hypertrophic response remained similar in HSPB2cKO and HSPB2wt hearts. In addition, mitochondrial respiration and ATP production assays demonstrated that the absence of HSPB2 did not change mitochondrial metabolism in basal conditions. However, fatty acid supported state 3 respiration rate (ADP stimulated) in TAC operated HSPB2cKO hearts was significantly reduced in compared with TAC operated HSPB2wt mice (10.5±2.2 vs. 12.8±2.5 nmol O(2)/min/mg dry fiber weight, P<0.05), and ATP production in HSPB2cKO hearts was significantly reduced in TAC compared with sham operated mice (29.8±0.2 vs. 21.1±1.8 nmol ATP/min/mg dry fiber weight, P<0.05). Although HSPB2 was not associated with mitochondria under cardiac stress, absence of HSPB2 led to changes in transcript levels of several metabolic and mitochondrial regulator genes.
  
  
  CONCLUSIONS
  The present study indicates that HSPB2 can be replaced by other members of the multigene small HSP family under basal conditions while HSPB2 is implicated in the regulation of metabolic/mitochondrial function under cardiac stress such pressure overload.
authors.affiliation: Laboratory of Cardiac Disease, Redox Signaling and Cell Regeneration, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishiwata
authors.forename: András
authors.initials: A
authors.lastname: Orosz
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Soumyajit Banerjee
authors.initials: SB
authors.lastname: Mustafi
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Pratt
authors.forename: Elisabeth S
authors.initials: ES
authors.lastname: Christians
authors.forename: Sihem
authors.initials: S
authors.lastname: Boudina
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Benjamin
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption
chemical_list: D055551:HSP27 Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D000255:Adenosine Triphosphate