Role of healing-specific-matricellular proteins and matrix metalloproteinases in age-related enhanced early remodeling after reperfused STEMI in dogs.
We assessed whether aging augments left ventricular (LV) damage, remodeling, and dysfunction and alters expression of healing-specific-matricellular proteins (HSMPs), matrix metalloproteinases (MMPs) and other pertinent proteins after acute reperfused-ST-segment-elevation myocardial infarction (RSTEMI) in the dog model. The findings suggest a novel role for HSMPs, MMPs, and the other proteins in the age-related increase in LV damage, remodeling, and dysfunction. Potentially detrimental effects of the altered proteins appear to outweigh beneficial effects and contribute to adverse outcome. Deleterious changes include the increase in matrix-degrading MMPs, inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, HSMPs such as secreted-protein-acidic-and-rich-in-cysteine (SPARC) and osteopontin (OPN), the blunted increase in endothelial-NOS (eNOS), and the decrease in IL-10 and neuronal NOS (nNOS). Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging.
Jugdutt
Bodh I
BI
Division of Cardiology, Department of Medicine, 2C2 Walter MacKenzie Health Sciences Centre, University of Alberta, Edmonton, AB, Canada. bjugdutt@ualberta.ca
Palaniyappan
Arivazhagan
A
Uwiera
Richard R E
RR
Idikio
Halliday
H
D000375:Aging; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism*; D015424:Reperfusion; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*; D014945:Wound Healing
D016207:Cytokines; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020782:Matrix Metalloproteinases