{"title":"Is neuropeptide Y really involved with regulating resting blood pressure?","authors":"Heidi A Kluess","doi":"10.1152/ajpheart.00791.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00791.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aram A Babakr, Mariana Angoa-Perez, Charles S Chung
{"title":"Is HFpEF a chicken or an egg? Utility of models for a clinical syndrom.","authors":"Aram A Babakr, Mariana Angoa-Perez, Charles S Chung","doi":"10.1152/ajpheart.00812.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00812.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acceleration of age-related impairments in vascular function in women: interrogation of the (un)usual hormonal suspects.","authors":"Kylee S West, Nathaniel D M Jenkins","doi":"10.1152/ajpheart.00730.2024","DOIUrl":"10.1152/ajpheart.00730.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1387-H1389"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shatha Salameh, Devon Guerrelli, Jacob A Miller, Manan Desai, Nicolae Moise, Can Yerebakan, Alisa Bruce, Pranava Sinha, Yves d'Udekem, Seth H Weinberg, Nikki Gillum Posnack
{"title":"Connecting transcriptomics with computational modeling to reveal developmental adaptations in pediatric human atrial tissue.","authors":"Shatha Salameh, Devon Guerrelli, Jacob A Miller, Manan Desai, Nicolae Moise, Can Yerebakan, Alisa Bruce, Pranava Sinha, Yves d'Udekem, Seth H Weinberg, Nikki Gillum Posnack","doi":"10.1152/ajpheart.00474.2024","DOIUrl":"10.1152/ajpheart.00474.2024","url":null,"abstract":"<p><p>Nearly 1% of babies are born with congenital heart disease-many of whom will require heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate drug therapies, and inform clinical care decisions related to surgical repair and postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we collected right atrial tissue samples from pediatric patients (<i>n</i> = 117) undergoing heart surgery. Patients were stratified into five age groups. We measured age-dependent adaptations in cardiac gene expression and used computational modeling to simulate action potential and calcium transients. Enrichment of differentially expressed genes revealed age-dependent changes in several key biological processes (e.g., cell cycle, structural organization), cardiac ion channels, and calcium handling genes. Gene-associated changes in ionic currents exhibited age-dependent trends, with changes in calcium handling (<i>I</i><sub>NCX</sub>) and repolarization (<i>I</i><sub>K1</sub>) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We observed a shift in repolarization reserve, with lower <i>I</i><sub>Kr</sub> expression in younger patients, a finding potentially tied to an increased amplitude of <i>I</i><sub>Ks</sub> that could be triggered by elevated sympathetic activation in pediatric patients. Collectively, this study provides valuable insights into age-dependent changes in human cardiac gene expression and electrophysiology, shedding light on molecular mechanisms underlying cardiac maturation and function throughout development.<b>NEW & NOTEWORTHY</b> To date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we demonstrate age-dependent adaptations in the gene expression profile of >100 atrial tissue samples collected from congenital heart disease patients. We coupled transcriptomics datasets with computational modeling to simulate action potentials and calcium transients for different pediatric age groups.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1413-H1430"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sex differences in the functional morphology of coronary arteries in embryonic mice.","authors":"Shion Nagasawa, Masami Kodama, Ryu Hagiwara, Kazuho Sakamoto, Koichi Nishiyama, Yuichiro Arima, Hiroki Kurihara, Junko Kurokawa","doi":"10.1152/ajpheart.00186.2024","DOIUrl":"10.1152/ajpheart.00186.2024","url":null,"abstract":"<p><p>Sex differences in the development and progression of cardiovascular disease manifest across multiple life stages. These differences are associated with variations in cardiovascular morphology and function between the sexes. Although estrogens and sex hormones are associated with sex differences in cardiovascular diseases in reproductive adults, the molecular mechanisms of cardiovascular sex differences during development are largely unknown. Thus, we investigated sex differences in cardiovascular development. We used a newly developed coronary arteriogram system to visualize the morphology of the coronary arteries in murine anterior surface ventricles at embryonic day 17.5 by injecting nanoparticle ink at a constant pressure. No sex difference was found in the length of ventricle. Based on the boundary value of the distribution of that length, the hearts were divided into \"long\" and \"short\" groups and the diameters of the left coronary arteries were analyzed. The mean diameter of the coronary arteries was significantly smaller in females than in males only in the group with the longer length of ventricle. This ventricular size-specific sex difference was observed in the presence of vasodilators such as NOC7 (1-Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene). When NOC7 was perfused into the left coronary arteries of embryonic day 17.5 mice, females with longer ventricles showed larger left coronary arteries than males. These sex differences in vasodilation capacity suggest that factors related to drug reactivity such as signaling pathways are present at a late embryonic stage. These results indicate that sex differences in the functional morphology of the left coronary arteries exist at a late embryonic stage in mice.<b>NEW & NOTEWORTHY</b> This study introduces a novel coronary angiography method for analyzing murine embryonic hearts, revealing sex differences in coronary artery morphology and contractile function in the late stage of the fetal period. By categorizing heart components based on size, we unveil nuanced insights into sexual dimorphism during this critical fetal period. This work contributes insights into the early origins of sexual dimorphism in coronary vessels, laying the foundation for further understanding of cardiovascular development.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1390-H1399"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongjun Lu, Elizabeth Kenkel, Kathy Zimmerman, Robert M Weiss, Robert D Roghair, Sarah E Haskell
{"title":"Sertraline-induced 5-HT dysregulation in mouse cardiomyocytes and the impact on calcium handling.","authors":"Yongjun Lu, Elizabeth Kenkel, Kathy Zimmerman, Robert M Weiss, Robert D Roghair, Sarah E Haskell","doi":"10.1152/ajpheart.00692.2023","DOIUrl":"10.1152/ajpheart.00692.2023","url":null,"abstract":"<p><p>Selective serotonin reuptake inhibitors (SSRIs) are prescribed in 15% of pregnancies in the United States for depression. Maternal use of SSRIs has been linked to an increased risk of congenital heart defects, but the exact mechanism of pathogenesis is unknown. SSRIs, including sertraline, are permeable to the placenta and can produce direct fetal exposure. Previously, we have shown decreased cardiomyocyte proliferation, left ventricle size, and cardiac expression of the serotonin receptor 5-HT<sub>2B</sub> in the offspring of mice exposed to the SSRI sertraline relative to the offspring of saline-exposed mice. Using a mouse model of in utero plus neonatal sertraline exposure, we observed lengthened peak-to-peak time of calcium oscillation (saline 784 ± 76 ms; sertraline 1,121 ± 130 ms, <i>P</i> < 0.001) and decreased expression of critical genes in calcium regulation. We also observed significant upregulation of specific microRNAs (miRNAs) that modulate serotonin signaling in neonatal cardiac tissues (<i>Slc6a4: miR-223-5p, miR-92a-2-5p, miR-182-5p; Htr2a: miR-34b-5p, miR-182-5p; Htr2b: miR-223-5p, miR-92a-2-5p, miR-337-5p</i>) (<i>P</i> < 0.05) with corresponding levels of the target mRNAs downregulated (<i>Slc6a4</i> 0.73 ± 0.05; <i>Htr2a</i> 0.67 ± 0.04; <i>Htr2b</i> 0.72 ± 0.03; all <i>P</i> < 0.01), resulting in decreased production of the cognate proteins. Adult mice at 10 wk showed altered cardiac parameters including decreased heart rates in males (saline 683 ± 8 vs. sertraline 666 ± 6 beats/min, <i>P</i> < 0.05) and ejection fraction in females (saline 83.9 ± 0.6% vs. sertraline 80.6 ± 1.1%, <i>P</i> < 0.05). These findings raise the question of whether sertraline exposure during development may increase the potential risk for cardiac disease when subjected to stress.<b>NEW & NOTEWORTHY</b> Sertraline exposure during development decreased the expression of critical genes in calcium regulation and lengthened periods in calcium oscillation in neonatal cardiomyocytes. Sertraline upregulated specific microRNAs that may modulate serotonin signaling in neonatal cardiac tissues, which corresponded with a decrease in the levels of the corresponding target mRNAs. Although the echocardiograms in our adult mice suggest a mild phenotype associated with sertraline exposure, these upregulated microRNAs (miRNAs) have been linked to adult cardiovascular disease and heart failure.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1559-H1576"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephen A Klassen, Jacqueline K Limberg, Ronée E Harvey, Chad C Wiggins, Julia E Spafford, Nathaniel J Iannarelli, Jonathon W Senefeld, Wayne T Nicholson, Timothy B Curry, Michael J Joyner, J Kevin Shoemaker, Sarah E Baker
{"title":"Human sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y bioavailability.","authors":"Stephen A Klassen, Jacqueline K Limberg, Ronée E Harvey, Chad C Wiggins, Julia E Spafford, Nathaniel J Iannarelli, Jonathon W Senefeld, Wayne T Nicholson, Timothy B Curry, Michael J Joyner, J Kevin Shoemaker, Sarah E Baker","doi":"10.1152/ajpheart.00639.2024","DOIUrl":"10.1152/ajpheart.00639.2024","url":null,"abstract":"<p><p>What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α<sub>2</sub>-adrenergic agonist, 10-min loading infusion of 0.225 µg·kg<sup>-1</sup>; maintenance infusion of 0.1-0.5 µg·kg·h<sup>-1</sup>) in six healthy individuals (5 females, 27 ± 6 yr). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (liquid chromatography-tandem mass spectrometry) levels at baseline and the dexmedetomidine maintenance infusion. Linear mixed-model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], <i>P</i> = 0.002), total AP clusters (β = 0.90 [0.22], <i>P</i> = 0.005), and AP frequency (β = 0.11 [0.03], <i>P</i> = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], <i>P</i> = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], <i>P</i> = 0.030) and AP frequency (β = 2.66 [0.81], <i>P</i> = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation.<b>NEW & NOTEWORTHY</b> The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α<sub>2</sub>-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1599-H1605"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Postnatal development of human atrial cardiomyocytes: linking atrial gene expression profiles and atrial electrophysiology.","authors":"Elise Rougier, Akshata Dhumal, Robert A Rose","doi":"10.1152/ajpheart.00754.2024","DOIUrl":"10.1152/ajpheart.00754.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1519-H1521"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A zebrafish model to study <i>RRAGD</i> variants associated cardiomyopathy.","authors":"Irene Sambri, Francesco Trepiccione","doi":"10.1152/ajpheart.00695.2024","DOIUrl":"10.1152/ajpheart.00695.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1343-H1344"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The multifaceted roles of red blood cells in health and disease.","authors":"Helmut Raphael Lieder","doi":"10.1152/ajpheart.00739.2024","DOIUrl":"10.1152/ajpheart.00739.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1474-H1476"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}