In This Issue

Abstract

HomeCirculation ResearchVol. 124, No. 4In 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 published14 Feb 2019https://doi.org/10.1161/RES.0000000000000262Circulation Research. 2019;124:451is related toWhole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of FallotOxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive DisorderAtherosclerotic Conditions Promote the Packaging of Functional MicroRNA-92a-3p Into Endothelial MicrovesiclesMajor Genetic Contributors to Tetralogy of Fallot (p 553)Download figureDownload PowerPointPage et al perform whole exome sequencing and identify genetic links to a common heart defect.Tetralogy of Fallot (TOF), a form of congenital heart defect, affects ≈1 in 3000 newborns. It is characterized by ventricular septal defect, pulmonary stenosis, right ventricular hypertrophy, and an overriding aorta. The condition is treated by surgery, which enables most patients to survive to age 30, but complications are common, as is premature death. The understanding of the pathology of TOF, however, is hindered by the fact that, in most cases, the underlying cause is unknown. Indeed, even though 15% of patients have a chromosomal deletion at 22q11.2 (often affecting the gene TBX1), 80% are nonsyndromic with generally no identifiable basis. Hence, to gain insight into additional underlying genetic contributors in TOF, Page and colleagues performed whole exome sequencing in 829 patients. Although they identified a large number of genetic variants in the participants’ DNA, strong associations were observed with only 2 particular genes—NOTCH1 and FLT4. Potentially pathological variations in NOTCH1, for example, were found in 4.5% of patients, and those in FLT4 were found in 2.5%. Interestingly, like TBX1, both NOTCH1 and FLT4 are important for blood vessel development, suggesting the root cause of TOF may be linked to problems with angiogenesis.Oxidant Stress and Endothelial Dysfunction in MDD (p 564)Download figureDownload PowerPointGreaney et al gather insights into depression-associated vascular dysfunction.Depression afflicts somewhere between 10% and 15% of the US population and is associated with a higher prevalence of cardiovascular disease (CVD), independent of traditional CVD risk factors. Nevertheless, the link between CVD risk and depression is unclear. Recent evidence suggests that major depressive disorder (MDD) is associated with heightened oxidative stress, as reflected by an increase in blood biomarkers of oxidative damage, reduced plasma levels of NO metabolites and endothelial dysfunction. To gain additional insights into the mechanisms underlying vascular dysfunction in depression, Greaney and colleagues examined 24 otherwise healthy MDD patients and 20 healthy controls. As expected, they found that biomarkers of oxidative stress were elevated in patients with MDD, but even though their vascular conductance (the ratio of blood flow to arterial pressure) in the cutaneous circulation was unaffected, both NO-dependent and -independent vascular dilation was blunted in MDD subjects. They also found that scavenging of superoxide, or inhibiting the production of reactive oxygen species, improved dilation in MDD patients. These finding suggest that strategies that target vascular oxidative stress may be a clinical option for reducing CVD risk in MDD.MicroRNA-92a-3p in Endothelial Microvesicles (p 575)Download figureDownload PowerPointMicroRNA-containing microvesicles alter endothelial cell function in atherosclerosis, report Liu et al.Coronary artery disease, resulting from atherosclerosis, is the leading cause of mortality worldwide. Among the many pathophysiological features of atherosclerosis is an increased abundance in the blood stream of microvesicles—small, cell-produced, membrane-bound packages containing proteins, messenger RNAs, and regulatory microRNAs that are thought to be important for cell-to-cell communication. To investigate the nature of these atherosclerosis-associated vesicles, Liu and colleagues compared circulating microvesicles from individuals with or without the condition. They found that microvesicles from individuals with atherosclerosis had higher levels of microRNA-92a-3b, than those from controls. Moreover, in their in vitro studies, they found that atherosclerotic stimuli promoted the production of miR-92a–filled microvesicles. These vesicles were also found to boost migration and proliferation of recipient endothelial cells. Indeed, knockdown of miR-92a-3b prevented such increased proliferation and migration, as well as vessel formation. The authors suggest that, in atherosclerosis, microvesicles containing miR-92a- may have regenerative potential that could be harnessed for therapeutic purposes. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesWhole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of FallotDonna J. Page, et al. Circulation Research. 2019;124:553-563Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive DisorderJody L. Greaney, et al. Circulation Research. 2019;124:564-574Atherosclerotic Conditions Promote the Packaging of Functional MicroRNA-92a-3p Into Endothelial MicrovesiclesYangyang Liu, et al. Circulation Research. 2019;124:575-587 February 15, 2019Vol 124, Issue 4 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000262 Originally publishedFebruary 14, 2019 PDF download Advertisement