Highlights From the Latest in Diabetes Research

Novel Mechanism Links Inflammation to Heart Failure

Numerous studies have demonstrated that markers of inflammation are linked to a variety of common chronic conditions, including diabetes, obesity, and cardiovascular disease. Despite the wealth of evidence suggesting that inflammation plays a causative role in heart disease, the underlying mechanisms by which an inflammatory state is initiated and maintained in the heart have been elusive. New data from Oka et al. suggest that mitochondrial DNA may be a key upstream player in the inflammatory response that is commonly observed in heart failure. This group’s previous work suggested that autophagy is an adaptive response that protects the heart under conditions of hemodynamic stress. Normally, mitochondria that are damaged by hemodynamic stress are handled by autophagy through the fusing of autophagosomes and lysosomes. The newly published data suggest that when mitochondrial DNAs evade this autophagic response in cardiomyocytes, they induce inflammation that can lead to myocarditis and cardiomyopathy. DNase II plays an important role in this process because it is known to degrade the DNA of apoptotic cells in the lysosome. In a series of experiments in which DNase2−/− and DNase2+/+ mice were exposed to transverse aortic constriction, DNase2−/− mice did not exhibit upregulation in DNase II activity, whereas DNase2+/+ mice responded to the increased pressure by upregulating DNase II. After 28 days, 57% of DNase2−/− mice died, compared to only 14% of DNase2+/+ mice. Finally, the hearts of the DNase2−/− mice showed cell infiltration and fibrosis, as well as upregulation of mRNA of both IL-6 and collagen. Notably, the investigators did not observe a difference in circulating levels of mitochondrial DNA, suggesting that the inflammatory response did not result from mitochondrial DNA in …

| Table of Contents
OPEN ACCESS ARTICLE

This Article

  1. doi: 10.2337/db12-dd08 Diabetes vol. 61 no. 8 2197-2198
  1. Free via Open Access: OA