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HomeCirculation ResearchVol. 107, No. 8In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Originally published15 Oct 2010https://doi.org/10.1161/RES.0b013e3181fd8052Circulation Research. 2010;107:939Mitochondria and Na+ Channels (p 967)Liu et al suggest a new way to prevent irregular heartbeats: by keeping a lid on mitochondrial ROS production.Download figureDownload PowerPointMaintaining a regular heartbeat depends on the correct functioning of the heart cells' sodium channels. Indeed, syndromes that display aberrant channel function, such as sudden infant death syndrome (SIDS) and Brugada syndrome, are associated with fatal heart arrhythmias. Both SIDS and Brugada syndrome are linked to gene mutations that result in an increase in the levels of NADH. Excessive NADH increases the intracellular production of reactive oxygen species (ROS), which it is believed might structurally damage the sodium channels. Liu et al were interested in discovering the origin of the ROS. Using a variety of chemical inhibitors, they ruled out certain cellular enzymes and molecules as the source and fingered the blame on mitochondria. When mitochondrial ROS production was inhibited, even in the presence of high cytosolic NADH, normal sodium channel conduction was restored. Therapies for SIDS, Brugada, and other arrhythmias have traditionally targeted the dysfunctional sodium channels themselves. The report by Liu et al suggests that an alternative or adjunctive approach might be to block ROS generation by the mitochondria.Enhanced Fibroblast–Myocyte Interactions (p 1011)Fibroblasts activated by heart injury do more than just form scars. They also directly interfere with heart cells' electrical activity, say Vasquez et al.Download figureDownload PowerPointAfter a heart injury, cardiac fibroblasts are activated and proliferate quickly to mend the damage. The resulting fibrotic scar was thought to affect the electrophysiology properties of the heart indirectly—by forming a boundary between electrically active muscle cells. But Vasquez and colleagues found that the activated fibroblasts are not so passive after all. A critical step in fibroblast activation is their conversion into myofibroblasts. Myofibroblasts differ from the normal cardiac fibroblasts in their proliferative, migratory, adhesive, and collagen-synthesizing capacities. It now appears they differ in their electrical properties, too. The team showed that compared with regular fibroblasts, myofibroblasts formed more connections with cardiomyocytes and altered the myocytes' conduction velocities and action potential durations. Interestingly, myofibroblast-conditioned culture medium could also affect myocyte electrical activity, indicating that myofibroblasts exert their affect both through cell-to-cell contacts and via secreted factors. Severe arrhythmias can ultimately result in sudden death. Because conversion of fibroblasts to myofibroblasts could potentially distort regular heart rhythm, targeting this conversion could be an effective antiarrhythmic strategy.DNA Damage in Atherosclerosis (p 1021)Damaged DNA drives development of atherosclerosis, report Mercer et al.Download figureDownload PowerPointDNA damage has been detected in the plaques and circulating cells of patients with atherosclerosis, but whether this damage was a byproduct or the antecedent cause of the disease was unknown. Mercer and colleagues now report data that support the latter possibility. The team showed that mice that were deficient for a DNA repair factor called ATM were prone to accelerated atherosclerosis and to other symptoms of metabolic syndrome, such as hypertension, increased body fat, and glucose intolerance. In the ATM-deficient mice, macrophages and vascular smooth muscle cells (VSMCs)—both of which contribute to plaque formation—displayed increased genomic and mitochondrial DNA damage, as well as increased reactive oxygen species (ROS) production. Transfer of bone marrow cells expressing wild-type levels of ATM improved the accelerated atherosclerosis phenotype. It did not improve the other symptoms, however, most likely because ATM-deficiency caused mitochondrial DNA damage and dysfunction in other tissues, such as liver and pancreas. Mitochondrial dysfunction might be particularly detrimental in metabolic syndrome progression because failing mitochondria produce excessive ROS, which can further damage DNA and worsen dysfunction. Drugs that reduce DNA damage or boost mitochondrial function, or both, could thus be especially effective in preventing atherosclerotic lesion formation and metabolic syndrome.Written by Ruth Williams Previous Back to top Next FiguresReferencesRelatedDetails October 15, 2010Vol 107, Issue 8 Advertisement Article InformationMetrics © 2010 American Heart Association, Inc.https://doi.org/10.1161/RES.0b013e3181fd8052 Originally publishedOctober 15, 2010 PDF download Advertisement