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Uncoupling Protein 3 Deficiency Impairs Contractile Recovery in a Rat Model of Myocardial Infarction and Reperfusion
Author(s) -
Mahmoudi Elena,
Lomax Tyler M.,
Harmancey Romain
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.830.7
Subject(s) - cardiology , medicine , myocardial infarction , ejection fraction , insulin resistance , endocrinology , ucp3 , heart failure , insulin , uncoupling protein , obesity , brown adipose tissue
Insulin resistance and diabetes are associated with poor prognosis following myocardial infarction and reperfusion (MI/R). Uncoupling protein 3 is a mitochondrial anion carrier which is down‐regulated by up to 50% in humans and animal models with obesity, insulin resistance, and type 2 diabetes. We previously reported that isolated hearts from Sprague Dawley rats which have been genetically modified to mimic this UCP3 deficiency (ucp3 +/− ) have poorer recovery of contractile function linked to an impairment of long‐chain fatty acid oxidation when subjected to ischemia/reperfusion. The goal of the present study was to extend these findings by investigating whether UCP3 deficiency similarly affects cardiac recovery in response to MI/R in vivo . Male ucp3 +/− rats (n=16) and their wild type ucp3 +/+ littermates (n=7) were subjected to 45 min MI by ligation of the left anterior coronary artery. Cardiac structure and function were assessed by echocardiography before surgery and at 2, 14, and 28 days following MI/R. On the 28 th day, left ventricular (LV) hemodynamic parameters were measured with a Millar pressure‐volume catheter. Masson's trichrome staining was then performed to measure the infarct size relative to LV area. The mortality rate at 24 hrs post MI/R was higher in ucp3 +/− rats (44%) when compared to the ucp3 +/+ controls (28%). At day 28 post MI/R, LV ejection fraction (22.6±1.5 vs. 36.6±2.9%), fractional shortening (10.9±0.7 vs. 19.8±1.2%). and LV end‐systolic anterior wall thickness (LVAWs; 1.3±0.1 vs. 2.0±0.1 mm) were all significantly decreased for the ucp3 +/− rats. Analysis of LV pressure‐volume loops also revealed greater impairment for −dP/dt min (1898+167 vs. 2832+380 mm Hg s −1 ), dP/dt max (1956±213 vs. 2981±219 mm Hg s −1 ), and for the LV relaxation time constant (Tau; 12.6±1.0 vs. 18.7±2.1 ms). The infarct size was also bigger for ucp3 +/− rats (52±4 vs. 26±4%). In summary, the results demonstrate that partial UCP3 deficiency is sufficient to impair functional recovery of the heart following MI/R in vivo . Future studies will determine whether the defect can be corrected by implementing therapeutic strategies aiming to improve fatty acid oxidation at reperfusion. Support or Funding Information This work was supported by NIH Grants R01HL136438, R00HL112952, P01HL051971, and P20GM104357. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .