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Late Preconditioning Induced by Transgenic Cardiac Overexpression of α1A Adrenergic Receptors in Rats
Author(s) -
Zhao Xin,
Park Jiyeon,
ho David,
Gao Shumin,
Yan Lin,
Ge hui,
Ilsmaa Siiri,
Lin Lin,
Tian Bin,
Vatner Dorothy,
Graham Robert,
Vatner Stephen
Publication year - 2012
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.26.1_supplement.1136.20
Subject(s) - cardioprotection , ischemic preconditioning , medicine , propranolol , adrenergic receptor , downregulation and upregulation , receptor , cardiology , myocardial infarction , transgene , endocrinology , chemistry , gene , ischemia , biochemistry
We determined the extent to which cardiac overexpression of the α 1A ‐adrenergic receptor (AR) in transgenic (TG) rats affords cardioprotection, and if it is involved in first or second window ischemic preconditioning (IPC). Without IPC, infarct size, induced by coronary artery occlusion (CAO) for 30min and 3hrs reperfusion (CAR; expressed as % area at risk), was reduced in TG vs. non‐transgenic littermates (NTL) (35±5% vs 50±2%, P<0.05). After 1 st window IPC, induced by 3 episodes of 5min CAO/5min CAR followed by 30min CAO/3hr CAR, infarct size of α 1A ‐AR TG was reduced further (12±1%) and was similar to NTL (10±1.1%). In contrast, 2 nd window IPC, induced by 3 episodes of 5min CAO/5min CAR followed by 30min CAO/3hr CAR at 24 hours after IPC, reduced infarct size only in NTL (29±3%), but not in TG (30±1%), suggesting that TG already exhibited 2 nd window IPC. Furthermore, blocking key molecules involved in 2 nd window IPC, (iNOS and the MEK/ERK pathway) abrogated cardioprotection in TG rats. Cardiac myocyte microarrays revealed that only 4.6% of 3172 upregulated and 8.8% of 3498 downregulated genes were directionally similar in α 1A ‐TGs without IPC compared to NTL with 2 nd window IPC. Thus, TG rats with cardiac α 1A ‐adrenergic receptor overexpression exhibit ischemic cardioprotection that resembles 2 nd window IPC, with only a minor fraction of overlapping genes.