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. Author manuscript; available in PMC: 2016 Jan 31.
Published in final edited form as: Biochim Biophys Acta. 2014 Jul 2;1852(2):232–242. doi: 10.1016/j.bbadis.2014.06.030

Figure 3. Progression of diabetic cardiomyopathy: role of oxidative/nitrosative stress, inflammation, cell death and remodeling.

Figure 3

The mechanisms leading to diabetic cardiomyopathy and failure are complex. Eventually the pathological alterations will result in mismatch between the load applied to the heart and the energy needed for contraction, leading to mechanoenergic uncoupling. After initial insults (episodes of hyperglycemia), secondary mediators such as angiotensin II (AII), norepinephrine (NE), endothelin (ET), proinflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α) and interleukin 6 and IL1β (IL-6 and IL1β), in concert with oxidative stress and peroxynitrite, activate downstream effectors (e.g., PARP-1 or MMPs)], act directly on the myocardium or indirectly via changes in hemodynamic loading conditions to cause endothelial and myocardial dysfunction, cardiac and vascular remodeling with hypertrophy, fibrosis, cardiac dilation, and myocardial necrosis, leading eventually to heart failure. The adverse remodeling and increased peripheral resistance further aggravate heart failure. MMPs, matrix metalloproteinases; PARP-1, poly(ADP-ribose) polymerase.