(849.15) Faster skin wound healing predicts survival after myocardial infarction

Poster Board Number: E15

Mediha Becirovic-Agic (University of Nebraska Medical Center, Nebraska-Western Iowa Health Care System), Upendra Chalise (University of Nebraska Medical Center, Nebraska-Western Iowa Health Care System), Mira Jung (Hannover Medical School), Jocelyn Rodriguez-Paar (University of Nebraska Medical Center, Nebraska-Western Iowa Health Care System), Shelby Konfrst (University of Nebraska Medical Center, Nebraska-Western Iowa Health Care System), Elizabeth Flynn (University of Mississippi Medical Center), Jeffrey Salomon (University of Nebraska Medical Center, University of Nebraska Medical Center), Michael Hall (University of Mississippi Medical Center), Merry Lindsey (University of Nebraska Medical Center, Nebraska-Western Iowa Health Care System)

Skin wound healing and the cardiac healing response to myocardial infarction (MI) both progress through similar pathways involving inflammation, resolution, tissue repair, and scar formation. Due to the similarities, we hypothesized that the healing response to skin wounding would predict future response to MI. Mice were given a 3 mm skin wound using a disposable biopsy punch, and the skin wound was imaged daily until closure. Wound closure was quantified using Image J software. The same set of mice was given MI by permanent coronary artery ligation 28 days later and followed for 7 days. Cardiac physiology (volume, dimension, ejection fraction, fractional shortening, wall thickness) was measured by echocardiography at baseline, and 3 and 7 days post MI. Mice that survived until MI day 7 were grouped as survivors (30 mice, 68%), and animals that died from MI were grouped as non-survivors (14 mice, 32%). Survivors had faster skin wound healing compared to non-survivors. Faster skin wound healing predicted MI survival better than commonly used cardiac functional variables (e.g., infarct size, fractional shortening, and end diastolic dimension). We mapped the plasma N-glycoproteome 3 days after skin wounding and 3 days after MI using mass spectrometry. The glycoproteome profile of MI day 3 plasma revealed alpha-2-macroglobulin and ELL-associated factor 1 as strong predictors of future MI death and progression to heart failure. A second cohort of MI mice validated these findings. In patients, alpha-2-macroglobulin was 1.7±0.3-fold elevated 48h after presentation of MI (p=0.009, 18 controls, 41 MI patients). The glycoproteome profile of plasma collected 3 days post skin wounding identified apolipoprotein D and vitamin D binding protein to mirror skin wound healing. Apolipoprotein D detrimentally regulated both skin and cardiac wound healing in part by promoting inflammation. Plasma levels of vitamin D binding protein and galectin 3 binding after skin wounding also predicted future MI dilation and progression to heart failure. Our results reveal that the skin is a mirror to the heart and common pathways link wound healing across organs.

National Institutes of Health grant U54GM115458 (MLL), National Institutes of Health grant HL137319 (MLL), Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development grant 5I01BX000505 (MLL), Swedish Society for Medical Research grant P19-0144 (MBA)