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Smooth muscle‐selective ablation of A‐kinase anchoring protein 150 (AKAP150) mitigates diabetes‐induced cardiac dysfunction
Author(s) -
Zhang Deqing,
Brittian Kenneth R,
Bhatnagar Aruni,
Nystoriak Matthew A
Publication year - 2019
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.2019.33.1_supplement.lb507
Subject(s) - medicine , endocrinology , diabetes mellitus , vascular smooth muscle , ejection fraction , aorta , diabetic cardiomyopathy , type 2 diabetes , cardiology , heart failure , cardiomyopathy , smooth muscle
Inadequate blood flow to the myocardium due to microvascular dysfunction may play a role in the development and progression of diabetic cardiomyopathy, although contributing mechanisms are poorly understood. Hyperglycemia, a hallmark of diabetes mellitus, promotes enhanced arterial tone via altered excitation‐contraction and ‐transcription coupling that is dependent upon kinase/phosphatase targeting to the membrane of vascular smooth muscle by the A‐kinase anchoring protein AKAP150. In this study, we tested the hypothesis that AKAP150‐dependent signaling in smooth muscle contributes to cardiac dysfunction in an experimental model of diabetes. We generated smooth muscle selective AKAP150‐null animals by crossing AKAP5‐floxed mice (Akap150 fl/fl ) with knock‐in mice expressing Cre recombinase under the control of SM22α (smCre). Offspring (AKAP150 fl/fl ‐smCre) were viable and demonstrated genetic recombination and loss of AKAP150 protein in vascular smooth muscle (aortic smooth muscle, mesenteric arteries, coronary arteries), but not in heart or brain tissues. Male AKAP fl/fl and AKAP fl/fl ‐smCre animals (8–12 weeks) were maintained on a high fat/high sucrose (HFHS) diet for 20 weeks. Body weight and blood glucose (fasting and non‐fasting) were significantly elevated in HFHS groups compared to control chow‐fed animals at time points after 8 weeks. At 20 weeks, echocardiography revealed that AKAP150 fl/fl animals on HFHS diet had significantly greater end systolic volume, as well as reduced ejection fraction and fractional shortening when compared to AKAP150 fl/fl mice maintained on control diet for the same period. However, no significant differences in cardiac function or chamber dimensions were observed between AKAP150 fl/fl ‐smCre animals on HFHS versus AKAP150 fl/f ‐smCre animals on control diet. Our results suggest that AKAP150‐mediated signaling in vascular smooth muscle may contribute to altered cardiac function in a HFHS model of diabetes. Support or Funding Information This work was supported in part by grants from the National Institutes of Health (GM103492, HL142710) and American Heart Association (16SDG27260070), This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .