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Astrocyte‐specific angiotensin II type 1 receptor knockout by using cre‐loxp system attenuates left ventricular remodeling after myocardial infarction (875.9)
Author(s) -
Isegawa Kengo,
Hirooka Yoshitaka,
Kishi Takuya,
Sunagawa Kenji
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.875.9
Subject(s) - astrocyte , glial fibrillary acidic protein , ventricular remodeling , medicine , endocrinology , receptor , myocardial infarction , biology , pathology , central nervous system , immunohistochemistry
Background: Brain angiotensin II type 1 receptor (AT 1 R)‐induced pathways (i.e., apoptosis, oxidative stress, and sympathoexcitation) worsen left ventricular (LV) remodeling after myocardial infarction (MI). Although astrocytes were recently suggested to have multiple and important functions in neurovascular unit, normal astrocytes have little AT 1 R. We hypothesized that MI‐induced abnormal expression of astrocyte AT 1 R, not neuron, would be a primary cause of worsening LV remodeling. Methods and Results: We generated astrocyte‐specific AT 1 R knockout mice (astrocyte/AT 1 R (‐/‐)). In astrocyte/AT 1 R (+/+) mice at 1 month after MI, we examined brainstem tissues by double immunohistostaining for glial fibrillary acidic protein (GFAP) and AT 1 R, and determined GFAP positive cells had morphologic changes with increased AT 1 R expression compared to sham mice without MI. In astrocyte/AT 1 R (‐/‐) at 1 month after MI, GFAP positive cells with AT 1 R expression were not observed. LV size at 1 month after MI was smaller in astrocyte/AT 1 R (‐/‐) than in astrocyte/AT 1 R (+/+) mice. Heart weight of astrocyte/AT 1 R (‐/‐) at 1 month after MI was lighter than that of astrocyte/AT 1 R (+/+) mice. Conclusion: Targeted deletion of AT 1 R in astrocytes attenuated LV dilatation after MI. These findings suggest that MI‐induced abnormal expression of AT 1 R in astrocytes is potential primary cause of worsening LV remodeling after MI.