Hypertension Editors’ Picks

HomeHypertensionVol. 77, No. 1Hypertension Editors’ Picks Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree BriefPDF/EPUBHypertension PicksPulmonary Hypertension The Editors Search for more papers by this author Originally published8 Dec 2020https://doi.org/10.1161/HYPERTENSIONAHA.120.14379Hypertension. 2021;77:e1–e10The following articles are highlighted as part of Hypertension’s series in pulmonary hypertension (PHT) from 2018 2020. While vasodilator therapies have produced significant improvement outcome patients with PHT, there remains morbidity associated condition. main reasons failure improve outcomes our incomplete understanding mechanisms underlying various forms emergence and recognition new subtypes the fact that some PHT do not proven dedicated therapeutic options, those do, efficacy available is frequently suboptimal. These gaps provide impetus further research directions PHT. studies referenced below been identified novel, contributing pathophysiology treatment Understanding predisposing vasoconstriction, smooth muscle proliferation, disease progression, thrombosis may allow development targets enhance ability treat Similar other cardiovascular conditions, differences microbiota, both airways gut, role ACE2 (angiotensin-converting enzyme 2) context help pathophysiology, while defining value vascular compliance prognostication. Pulmonary vasoconstriction endothelial dysfunction result effects cyclophilin A 15-HETE on cell function, long noncoding RNAs hypoxia, regulatory circ-calm4/myosin 10 axis or abnormalities potassium channel function. Animal hypoxia-induced mitogenic factor suggest a cardiac hypertrophy calcium-mediated proliferation remodeling. risk developing arterial prognosis condition be influenced release HMGB1 (high mobility group box 1) dimers males, intrauterine growth restriction via sperm epigenetic modifications, circulating levels sex hormones, particular, estradiol. In terms therapy, models improving sildenafil delivery artery cells, using glucuronic acid–modified lysosomes, well types extracellular vesicles deliver therapy potential techniques efficacy. Decreased OLA1 (Obg-like ATPase-1) expression newborn also represent target. Key review cover important aspects PHT: clinical due left heart disease, roles endothelin, ATP-sensitive channels, modulations, RNAs. It clear that, despite progress options it one less well-understood states limited long-term poor outcomes.Necrosis-Released (High Mobility Group Box Progressive Arterial Associated With Male Sex1AbstractDamage-associated molecular patterns, such 1), play well-recognized (PAH)—a progressive fatal vasculature. However, contribution particular type death, form released PAH unclear. Moreover, although male show higher level HMGB1, its involvement severe phenotype reported males unknown. study, we aimed investigate sources active damaged cells their males. Our results showed either human underwent necrotic only produce during apoptosis. death induced dimeric found mitochondrial reactive oxygen species dependent, TLR4 (toll-like receptor 4) activation. modified Sugen/hypoxia rat model replicates sexual dimorphism severity (right ventricular systolic pressure versus females, 54.7±2.3 44.6±2 mm Hg). By model, confirmed necroptosis necrosis primary rats, increased circulation dimers. Attenuation but apoptosis prevented activation blunted severity. We conclude necrosis, through dimers, predisposes PAH.Altered Airway Microbiota Composition Patients Hypertension2AbstractAlteration microbiota composition respiratory tract has progression many chronic lung diseases; yet, correlation causal link between (PH) remain largely This study aims define compare pharyngeal swab samples PH reference subjects. total 118 79 subjects were recruited, collected sequence 16S ribosomal RNA V3-V4 region microbiome. relative abundances profoundly different Ace Sobs indexes indicated richness pharynx significantly higher; community diversity markedly lower PH, comparing profile two groups principal component analysis. linear discriminant analysis effect size revealed proportion Streptococcus, Lautropia, Ralstonia than output, which represents microbial gene functions, genes related bacterial invasion epithelial toxins enhanced, energy metabolism, protein digestion absorption, division pathways attenuated summary, reports first systematic definition divergent upper subjects.Predictive Value Compliance Systemic Lupus Erythematosus Hypertension3AbstractPulmonary serious complication systemic lupus erythematosus. characterized right afterload, mainly comprises (PAC) resistance. PAC predicting erythematosus–associated investigated yet. Between February 2012 December 2016, 120 consecutive diagnosed based catheterization enrolled, prospectively. Baseline characteristics hemodynamic assessment analyzed. afterload was stratified according end point composite all-cause mortality worsening. Among them, points occurred 49 (41%) after 15 months (interquartile range, 8.5–24.0). <1.39 mL/mm Hg had 3.09-fold ([95% CI, 1.54–6.20] P=0.001) events ≥1.39 Hg. Multivariable Cox regression independent predictor (hazard ratio, 2.009 [95% 1.390–2.904]; P<0.001). 3-group prediction created. highest (PAC, Hg; resistance, ≥10.3 Wood units) (χ2, 6.10; P<0.014) experiencing point. good worsening hypertension. PAC, addition an attractive tool screening high-risk populations these patients.CAR (CARSKNKDC) Peptide Modified ReNcell-Derived Extracellular Vesicles Novel Therapeutic Agent Targeted Therapy4AbstractIn recent years, mesenchymal stem (MSC)–derived (EVs) emerging agent (PH). full realization MSC-derived EV hampered absence standardization MSC culture challenges industrial scale-up. exploit alternative replacement MSCs currently commercialized lines effective targeted therapy. ReNcell VM—a neural line—has utilized here reliable easily adoptable source EVs. demonstrated ReNcell-derived (ReNcell-EV) pretreatment effectively Su/Hx (SU5416/hypoxia)-induced mice. Then conjugated ReNcell-EVs CAR peptide (CAR-EVs)—a specifically target hypertensive arteries, bio-orthogonal chemistry. Intravenous administration CAR-EVs selectively lesions, especially cells. compared unmodified ReNcell-EVs, CAR-EV improved reversing Su/Hx-induced Mechanistically, inhibited migration, switch at least part, endogenous highly expressed miRNAs, let-7b-5p, miR-92b-3p, miR-100-5p. addition, endothelial-mesenchymal transition microvascular Taken together, EV–based Particularly, CAR-conjugated EVs serve novel drug carrier enhances specificity efficiency PH-targeted therapy.Uncovered Contribution Kv7 Channels Vascular Tone Hypertension5AbstractK(+) channels fundamental regulating membrane (PA) impairment common feature PA (PAH). K(+) voltage-gated subfamily Q (KCNQ1-5) subunit E (KCNE) subunits known regulate tone, whether function impaired how can affect rationale targeting Here, studied Kv7/KCNE possible alteration PAH. Using patch-clamp technique, current reduced animals (SU5416 plus hypoxia) currents made net current. Likewise, enhanced responses modulators rats. Accordingly, KCNE4 upregulated lungs patients. Additionally, activity presence Kv1.5 TASK-1 inhibitors, abundance. Compared response modulators, abundance Kv7.4 KCNE4. data indicate preserved Therefore, downregulated PAH, resulting sensitivity modulators. provides insight into usefulness PAH.Long Noncoding Rps4l Mediates Proliferation Hypoxic Artery Smooth Muscle Cells6AbstractPulmonary rare disorder involving remodeling arteries mediated (PASMCs). Long subclass molecules diverse cellular unexplored. identify determine functions involved PASMC proliferation. sequencing hypoxic mouse hypoxia-regulated RNAs, including Rps4l. PH-model mice PASMCs. subcellular localization detected fluorescence situ hybridization quantification nuclear/cytoplasmic RNA. overexpression rescued features, ventricle hypertrophy, pressure, hemodynamics, At level, weakened viability suppressed cycle progression. Potential Rps4l-binding proteins pull-down followed mass spectrometry, immunoprecipitation, microscale thermophoresis. affects stabilization ILF3 (interleukin enhancer-binding 3). Rps41 regulates HIF (hypoxia-inducible factor)-1α consequently leads migration. PASMCs, decreases regulation hypoxia. decrease PASMCs ILF3/HIF-1α. theoretical basis investigations pathological mechanism treatments.Endothelial-to-Mesenchymal Transition Inflammation Play Roles Cyclophilin A-Induced Hypertension7AbstractOxidative stress inflammation key previously (EC)–specific developed stimulates inflammation, responsible defined. endothelial-to-mesenchymal A–mediated studied. neointimal animal models. EC-specific exhibited features characteristic lineage tracing high-level markers ECs. number media perivascular regions arterioles alveoli derived ECs isolated phenotypic changes culture. Cultured stimulated acetylated functional cytokine release, dysfunction. Acetylated greater increases most transition. conclusion, (especially form) contributes transition, EC dysfunction, strengthening studying inhibition PAH.Oral 15-Hydroxyeicosatetraenoic Acid Induces Mice Triggering T Cell-Dependent Endothelial Cell Apoptosis8AbstractPulmonary (PAH) mean pressure. Elevated plasma concentrations oxidized lipids, 15-HETE, feeding sufficient induce hypertension, diet antigen processing presentation cell-mediated cytotoxicity. Analysis microarray identical controls. 15-HETE–fed immunoproteasome 5 increased, concomitant increase CD8 (cluster differentiation 8)/CD69 69) double-positive Human cultured prone when exposed intestinal secreted lipids consistent accumulation Administration apoA-I (apolipoprotein A-I) mimetic peptide, Tg6F (transgenic 6F), prevent 15-HETE–induced (1) induces involves lipid-mediated cell-dependent (2) treating PAH.Gut Pathology Its Rescue (Angiotensin-Converting Enzyme Hypoxia-Induced Hypertension9AbstractTherapeutic advances incremental because focus vasculature pathology. evaluate concept is, rather, interplay among multiorgan systems, brain, lungs. objective hypothesis dysfunctional brain-gut-lung global rebalances protects against PH. knockin WT (wild type; C57BL/6) subjected hypoxia (10% FIO2) room air 4 weeks. Cardiopulmonary histology, immunohistochemistry, fecal rRNA analyses evaluated. Hypoxia sympathetic activity, microglia paraventricular nucleus hypothalamus muscularis layer thickening villi length goblet altered gut microbiota. Global established distinct communities Furthermore, matter transfer resistant controls receiving transfer. observations demonstrate ameliorates pathologies attenuates implicate communication avenues interventions.ACE2 2)-Mediated Protection From Hypertension: Lung-Gut Axis Center Stage10ExtractACE2 multidimensional transmembrane monocarboxypeptidase, regulator amino acid transport, SARS-CoV-2 receptor. place central orchestrator controlling renin-angiotensin system, coronavirus 2019 (COVID-19) pandemic, respectively. culminate hypertension.Pulmonary Due Left Heart Disease: Diagnosis, Pathophysiology, Therapy11AbstractPulmonary (LHD) defined >20 capillary wedge >15 catheterization. LHD lead elevated atrial alone, intrinsic will without Persistent elevation may, however, subsequent remodeling, Hence, 2 subgroups LHD, postcapillary combined post- precapillary differing implications. Differentiation critical guide management planning; challenging. Older patients, metabolic syndrome, imaging suggestive etiology rather Hemodynamic measures diastolic gradient, transpulmonary resistance assist differentiate pre- offer prognostic insights. fluid status treatment. trialed concerning reflecting heterogeneity, variation inclusion criteria, mixed criteria. aim updated discuss aspects, LHD.Effects Chronic Nicotine Inhalation Blood Pressure Right Ventricular Remodeling Mice12AbstractCigarette smoking single nicotine pathogenesis diseases incompletely understood. purpose examine inhalation blood C57BL6/J (control) vapor (daily, 12-hour on/off) 8 recorded weekly radiotelemetry, monitored echocardiography. weeks, measure (RV) Nicotine-exposed weeks 1 3, then returned baseline 8, indicating tolerance nicotine. RV nicotine-exposed Echocardiography 8-week resulted free wall thickness trend internal diameter. contrast, no structural exposure. observed angiotensin-converting mitogen-activated kinase ventricle. alters latter accompanied possibly leading persistent hypertension.Altered Gut Microbiome Profile Hypertension13AbstractPulmonary considered Limited preventing arresting extensive efforts. previous could since pathology multiple organs. This, coupled increasing implication microbiome diseases, led us hypothesize exhibit to, predicts, disease. Fecal 18 (mean 57.4; SD, 16.7 Hg) 13 shotgun metagenomics hypothesis. Significant taxonomic cohort observed. Pathways synthesis arginine, proline, ornithine cohort. trimethylamine/trimethylamine N-oxide purine metabolism butyrate- propionate-producing bacteria Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia, Bacteroides random forest predicted 83% accuracy. Finally, virome enrichment enterococcal depletion lactococcal phages unique high predictive highlights unknown therapeutic, diagnostic, paradigms PAH.Circ-Calm4 Serves miR-337-3p Sponge Regulate Myo10 (Myosin 10) Promote Proliferation14AbstractPulmonary Recent circular (circRNA) biological processes, circRNA present circRNAs clarify 67 differentially tissues Screening bioinformatics quantitative polymerase chain reaction splicing calm4 (calmodulin (designated circ-calm4). Notably, absorbed miR-337-3p. (myosin bound 3′-untranslated mRNA, thereby attenuating translation Myo10. loss-of-function gain-of-function approaches, circ-calm4 regulated cycle. verified muscle. suggested circ-calm4/miR-337-3p/Myo10 signal transduction modulated thus establishing early diagnosis hypertension.Endothelin: 30 Years Discovery Therapy15AbstractDiscovered 1987 potent cell–derived vasoconstrictor ET-1 (endothelin-1)—the predominant member endothelin family—is now recognized multifunctional cytokine-like almost all physiology More 000 scientific published over past 3 decade