medwireNews: Results of a preclinical study confirm that microvascular destabilization caused by diabetes exacerbates cardiac ischemic damage, but this damage may be partially combated with treatment to induce neovascularization.
Christian Kupatt (Technical University Munich, Germany) and colleagues demonstrated reduced myocardial tissue density and pericyte loss in combination with reduced contractility and increased wall stiffness in hearts from transplant patients with versus without diabetes, which confirmed “a correlation between microvascular disturbance and dysfunction.”
Similarly, in a diabetic pig model, hyperglycemia was associated not only with reduced myocardial tissue density, but also with impaired ejection fraction (EF; 44.9 vs 53.4% in wild-type pigs) and decreased functional reserve. And capillary density and EF both decreased further in diabetic than wild-type pigs under chronic ischemia.
Treatment of the diabetic pigs with thymosin beta 4 (Tβ4) gene therapy induced neovascularization and improved EF compared with control treatment, but these improvements were “less pronounced” than those seen with Tβ4 treatment in the hearts of wild-type pigs, say Kupatt and team in the Journal of the American College of Cardiology.
The author of an accompanying editorial comment Kiyotake Ishikawa (Icahn School of Medicine at Mount Sinai, New York, USA) highlights the importance of preclinical research in large animals “to increase the probability of success in translating promising novel therapies” into the clinic.
He notes that the transgenic pig model used in the present study had low levels of circulating insulin, and so was “similar to type 1” diabetes, but was not reflective of type 2 diabetes.
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