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Novel roles of chromogranin A and its peptide, catestatin, in cardioprotection (652.3)
Author(s) -
Schilling Jan,
Avolio Ennio,
ZemljicHarpf Alice,
Headrick John,
Fridolfsson Heidi,
Kassan Adam,
Bandyopadhyay Gautam,
Siddiqui Jawed,
O'Connor Daniel,
Roth David,
Patel Hemal,
Mahata Sushil
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.652.3
Subject(s) - cardioprotection , chromogranin a , insulin , insulin resistance , medicine , endocrinology , endogeny , ischemia , immunohistochemistry
Chromogranin A (Chga) is abundant in (neuro) endocrine cells, and its derived peptide catestatin (CST) acts as an antihypertensive, cardioprotective, pro‐angiogenic, and insulin‐sensitizing peptide. The role of Chga and CST in ischemic preconditioning (IPC), an endogenous cardioprotective response, is unknown. We hypothesized that CST in the setting of diet‐induced insulin‐resistance would modulate the response of the heart to IPC. We used wild‐type (WT), Chga knockout (KO) and CST KO mice. Animals were fed normal chow (NCD) and 60% high fat diet (HFD for 3 months). IPC‐induced cardioprotection was abolished in both NCD and HFD fed CST‐KO mice, implicating a novel role for CST in IPC. Decreased phosphorylation of Akt and GSK‐3β in CST‐KO mice suggests involvement of the RISK pathway. HFD diminished cardiac performance (by 蠅50%) in all strains of mice. Interestingly, IPC in NCD and HFD Chga‐KO mice induced cardioprotection despite increased ventricular mass and wall thickness in NCD and increased weight gain (>25%) after HFD. Chga‐KO mice differed from CST‐KO mice in being sensitive to insulin even after HFD as assessed by insulin tolerance test and insulin clamp studies, indicating a novel role of insulin sensitivity in cardioprotection. We conclude that the presence of CST and maintenance of insulin sensitivity are two obligatory requirements for achieving cardioprotection from I/R injury through IPC.