Abstract

HomeCirculation ResearchVol. 123, No. 9In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published11 Oct 2018https://doi.org/10.1161/RES.0000000000000232Circulation Research. 2018;123:1009is related toLactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery DiseaseRestoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in Adultsis related toMidbody Positioning and Distance Between Daughter Nuclei Enable Unequivocal Identification of Cardiomyocyte Cell Division in MiceUnequivocal Identification of Cardiomyocyte Division (p 1039)Download figureDownload PowerPointHesse et al devise a new method for assessing cardiomyocyte proliferation.A myocardial infarction can lead to the death and destruction of a significant number of heart cells that, due to the limited regenerative capacity of the heart, do not regrow. Scientists are, therefore, vigorously searching for pharmacological agents that can induce the proliferation of cardiomyocytes and regrowth of the myocardium. The gold-standard marker of cell proliferation in vitro is Aurora B-kinase, but Hesse and colleagues argue that this poses a problem in the case of cardiac myocytes, many of which are binucleated. Indeed, Aurora B-kinase-based assays do not differentiate between binucleation and true cell division, the researchers show. The team, therefore, proposes an alternative marker—the positioning of the midbody and the distance between daughter nuclei. Using time-lapse microscopy to image cells from mice expressing fluorescently labeled anillin (a midbody protein), they observed that while true division resulted in symmetrical positioning of the midbody between daughter nuclei, binucleation was marked by randomly located and fragmented midbodies. Furthermore, in binucleation, but not true division, the daughter nuclei remained close together, almost touching. The authors suggest adopting this new strategy could provide a more accurate indication of real proliferation.Dhh Agonists Ameliorate Endothelial Function (p 1053)Download figureDownload PowerPointA Dhh agonist improves vascular function in mice with critical limb ischemia, report Caradu et al.Dysfunction of the vascular endothelium, which can result in leaky, inflamed blood vessels, is often associated with hypertension, diabetes, obesity, and advanced age. Although the pathways leading to endothelial dysfunction are largely unknown, it has been shown that the transcription factor Klf2, essential for endothelial health, is down-regulated in the context of vascular inflammation, high glucose, and disturbed blood flow. And recently, it was shown that morphogen Dhh is suppressed under similar conditions. Intrigued by this apparent coregulation, Caradu and colleagues tested whether Klf2 and Dhh might work in the same pathway. Indeed, they found that Klf2 directly activates the Dhh promoter. Moreover, knock-down of Dhh produced effects similar to those of Klf2 suppression—namely vessel leakiness and increased expression of proinflammatory factors. The team also found that critical limb ischemia is associated with capillary leakage and inflammation in both human patients and mice, and that treatment of the animals with a Dhh agonist could improve endothelial function. Together, the results imply that boosting the Klf2-Dhh pathway might be an effective approach for treating ischemic vascular disease.L Plantarum 299v and Endothelial Function (p 1091)Download figureDownload PowerPointProbiotic treatment improves vascular health in patients with coronary artery disease, report Malik et al.Atherosclerosis and plaque instability have been found to be associated with differences in the microbial composition of the human gut—both in terms of specific species and their diversity. Furthermore, in mice, fecal transfers, antibiotics, and high-fiber diets—all of which can alter the gut microbiome—have been shown to influence vascular health, systemic inflammation, and atherogenesis. Despite this evidence, it is unclear whether treatments that target the microbiome improve human vascular health. To find out, Malik et al gave Lactobacillus plantarum 299v (Lp299v)—a gut microbe shown to have positive cardiovascular effects in animals and human smokers—to 20 men with coronary artery disease. They found that daily treatments for 6 weeks reduced the levels of proinflammatory cytokines in the blood and improved vasodilation in the brachial arteries. Additionally, plasma taken from the subjects after treatment was shown to improve acetylcholine-induced dilation in CAD patient arterioles in tissue culture. The findings suggest that probiotic supplementation might be an additional tool for reducing cardiovascular disease risk, and open the door for further large-scale probiotic trials. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesLactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery DiseaseMobin Malik, et al. Circulation Research. 2018;123:1091-1102Midbody Positioning and Distance Between Daughter Nuclei Enable Unequivocal Identification of Cardiomyocyte Cell Division in MiceMichael Hesse, et al. Circulation Research. 2018;123:1039-1052Restoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in AdultsCaroline Caradu, et al. Circulation Research. 2018;123:1053-1065 October 12, 2018Vol 123, Issue 9 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000232PMID: 30355170 Originally publishedOctober 11, 2018 PDF download Advertisement

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