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Improved cardiac remodeling after in vivo knockdown of type VI collagen following myocardial infarction
Author(s) -
Baker Nicholas J.,
Minasyan Ashot,
Adapala Ravi,
McShannic Christian M.,
Gan Connie,
Hom Brian L.,
Thodeti Charles K.,
Meszaros J. Gary
Publication year - 2018
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.2018.32.1_supplement.867.2
Subject(s) - gene knockdown , in vivo , medicine , myocardial infarction , cardiology , cardiac function curve , ejection fraction , myocyte , infarction , cardioprotection , ventricular remodeling , apoptosis , heart failure , chemistry , biology , biochemistry , microbiology and biotechnology
Rationale Our previous studies have shown that hearts of Col6 −/− mice are protected from myocardial infarction (MI) injury, as these hearts exhibit reduced myocyte apoptosis, fibrosis and wall thinning leading to preserved long‐term cardiac function. The current project was designed to test whether knockdown of Col6 is feasible in the rat MI model and carries a similar cardioprotective effect during post‐MI remodeling. Objective To utilize a novel, non‐viral delivery method to deliver and determine whether siRNA‐mediated knockdown of Col6 is effective in the infarcted rat heart and affords cardioprotection in vivo in the weeks following MI injury. Methods and Results MI was induced via ligation of the left anterior descending artery (LAD) in adult Sprague‐Dawley rats and cardiac function was measured by transthoracic echocardiography. Calculated changes in endocardial volume, percent ejection fraction (%EF), and percent fractional shortening (%FAC) were performed at 1–6 weeks post‐MI. We witnessed a decrease in mean endocardial %EF of 44.7 ± 1.4 % in vehicle treated (control) rats, a parameter that was higher in siRNA treated hearts at 47.4 ± 1.8 %. A similar improvement was also seen in endocardial %FAC, which was 30.1 ± 1.4 % in vehicle treated rats versus 34.0 ± 1.3 % in siRNA treated rats. Knockdown of Col6 in vivo resulted in lower endocardial diastolic volume in siRNA treated rats (654.1 ± 81.3 μl in the vehicle group compared to 549.8 ± 8.4 μl for the siRNA treated group) and lower systolic volume in siRNA treated rats (362.7 ± 49.9 μl in the vehicle group compared to 291.6 ± 9.6 μl in the siRNA treated group). Conclusions siRNA mediated Col6 knockdown using JET‐PEI as a novel delivery method was effective in vivo , reducing Col6 expression levels over 75% in the anterior wall of the LV. Echocardiography revealed that the siRNA injections preserved cardiac function and prevented left ventricular chamber dilation following MI, indicating that this approach may have a positive therapeutic benefit in the recovery from MI injury. Support or Funding Information NIH R15HL132312 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .