American journal of physiology. Heart and circulatory physiology最新文献

{"title":"Sex Differences in Aortic Valve Inflammation and Remodeling in Chronic Severe Aortic Regurgitation.","authors":"Carolina Tiraplegui, Mattie Garaikoetxea Zubillaga, Alba Sádaba, Susana San Ildefonso-García, Miriam Goñi-Olóriz, Amaya Fernández-Celis, Ernesto Martin-Nuñez, Virginia Álvarez, Rafael Sádaba, Vidhu Anand, Eva Jover, Adela Navarro, Natalia López-Andrés","doi":"10.1152/ajpheart.00645.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00645.2024","url":null,"abstract":"<p><p><b>Background:</b> Aortic regurgitation (AR) is more prevalent in male, although cellular and molecular mechanisms underlying the sex differences in prevalence and pathophysiology are unknown. <b>Objectives:</b> This study evaluates the impact of sex on aortic valve (AV) inflammation and remodeling as well as the cellular differences in valvular interstitial cells (VICs) and valvular endothelial cells (VECs) in patients with AR. <b>Methods:</b> A total of 144 patients (27.5% female) with severe chronic AR were included. AVs were analyzed by imaging, histological and molecular biology techniques (ELISA, RT-PCR). VICs and VECs isolated from patients with AR were characterized and further treated with transforming growth factor (TGF)-β. <b>Results:</b> Anatomically, male had smaller index aortic dimensions and greater AV thickness. Proteome profiler analyzes in AVs (n=40/sex) evidenced higher expression of inflammatory markers in male and that was further validated (interleukins, chemokines). Histological composition showed higher expression of inflammatory mediators and collagen thick fibers in AVs from male. Male VICs and VECs secreted higher levels of inflammatory markers than female cells. Interestingly, male VICs produced higher amounts of collagen type I and lower fibronectin and aggrecan, whereas male VECs secreted lower decorin. TGF-β exclusively enhanced inflammation in male VICs, and decorin and aggrecan in female VICs. <b>Conclusion:</b> Compared to male, AVs from female were thinner, less inflamed and fibrotic. VIC seem to be the key cell type responsible for the sex-differences. Valvular inflammation associated with an active remodeling process could be a key pathophysiological process involved in AR.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976991","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":"High variability in the reproducibility of key hemodynamic responses to head-up tilt.","authors":"Heidi Bouquin, Lauri J Suojanen, Jenni K Koskela, Essi Pietilä, Manoj Kumar Choudhary, Jukka T Mustonen, Ilkka H Pörsti","doi":"10.1152/ajpheart.00796.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00796.2024","url":null,"abstract":"<p><p>Increased blood pressure upon standing is considered a cardiovascular risk factor. We investigated the reproducibility of changes in aortic blood pressure, heart rate, stroke volume, cardiac output, and systemic vascular resistance during three passive head-up tilts (HUT) in 223 participants without cardiovascular medications (mean age 46 years, BMI 28 kg/m2, 54% male). Median time gap between the first and the second HUT was 9 weeks and the second and the third HUT 4 weeks. We utilized whole-body impedance cardiography and radial artery tonometry as methods. The participants were divided into quartiles of the changes in each hemodynamic variable during the first HUT, and the reproducibility of these changes was tested during successive HUTs. During the first HUT, significant differences were present in all between-quartile comparisons (n=6) of all variables. The differences persisted as follows: reduction of stroke volume in six out of six (6/6) between-quartile comparisons (p<0.001), decrease in cardiac output (p<0.001) and increase in heart rate in 5/6 comparisons (p<0.001), change in systemic vascular resistance in 3/6 comparisons (p<0.001), change in aortic systolic blood pressure in 1/6 comparisons (p=0.043), and change in aortic diastolic blood pressure in none (p=0.266). To conclude, the reproducibility of upright posture-induced changes is high for stroke volume, cardiac output, and heart rate, moderate for systemic vascular resistance, and modest for aortic blood pressure. While an increase in blood pressure during upright posture may be a cardiovascular risk factor, this effect may be attributed to other underlying hemodynamic variables that exhibit more reproducible posture-related changes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942654","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":"Serial and regional assessment of the right ventricular molecular and functional response to pressure loading.","authors":"Kana Yazaki, Michael Dewar, John Dauz, Yohei Akazawa, Lucy Hui, Mei Sun, Wei Hui, Golam Kabir, Jean-Francois Dejardin, Kim A Connelly, Scott P Heximer, Mark K Friedberg","doi":"10.1152/ajpheart.00322.2024","DOIUrl":"10.1152/ajpheart.00322.2024","url":null,"abstract":"<p><p>Right ventricular (RV) function determines outcomes in RV pressure loading. A better understanding of the time-course and regional distribution of RV remodeling may help optimize targets and timing for therapeutic intervention. We sought to characterize RV remodeling between zero and 6 wk after the initiation of RV pressure loading. Thirty-six rats were randomized to either sham surgery or to pulmonary artery banding (PAB). After echocardiography and conductance catheter studies, groups of rats were euthanized at 1 wk, 3 wk, and 6 wk after sham surgery, or induction of RV pressure loading, for RV histological, RNA, and molecular analysis. A vigorous inflammatory response characterized by increased RV inflammatory cytokines, chemokines, and macrophage markers was observed at 1 wk following PAB. Metabolic changes, transforming growth factor-β (TGF-β)1 canonical signaling, collagenous fibrosis deposition, and apoptosis were already significantly increased by 1 wk after PAB. Genes marking fibroblast activation were upregulated at 1 wk but not at 6 wk post-PAB surgery. Mitochondrial dysfunction was evidenced by increased pyruvate dehydrogenase kinase (PDK) activity and decreased pyruvate dehydrogenase (PDH) phosphorylation significantly at 6-wk post-PAB. These processes preceded the development of overt myocardial hypertrophy and impaired echo parameters of systolic and diastolic function that occurred significantly from 3 wk after PAB. RV myocardial inflammation, metabolic shift, metabolic gene transcription, and profibrotic signaling occur early after initiation of pressure loading when RV pressures are only moderately elevated, before the development of overt myocardial hypertrophy and dysfunction, suggesting that adaptive hypertrophy and maladaptive remodeling occur simultaneously. These results suggest that therapeutic intervention to reduce adverse RV remodeling may be needed earlier and at lower thresholds than currently used.<b>NEW & NOTEWORTHY</b> Exploring the dynamics of right ventricular remodeling: unveiling the intricate interplay between inflammation, metabolic shifts, and fibrotic signaling in response to pressure loading. Through a comprehensive study spanning from initiation to 6 wk post-pressure loading, our research sheds light on the early onset of crucial molecular processes preceding overt hypertrophy and dysfunction. These findings challenge conventional intervention timing, advocating for early, targeted therapeutic strategies to mitigate adverse remodeling in right ventricular pressure loading.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H58-H74"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456048","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":"MicroRNA in pediatric pulmonary hypertension microRNA profiling to inform disease classification, severity, and treatment response in pediatric pulmonary hypertension.","authors":"Michael A Smith, Sam Chiacchia, Jason Boehme, Sanjeev A Datar, Emily Morell, Roberta L Keller, Amy Romer, Elizabeth Colglazier, Claire Parker, Jasmine Becerra, Jeffrey R Fineman","doi":"10.1152/ajpheart.00622.2024","DOIUrl":"10.1152/ajpheart.00622.2024","url":null,"abstract":"<p><p>Pediatric pulmonary hypertension is a heterogeneous disease associated with significant morbidity and mortality. MicroRNAs have been implicated as both pathologic drivers of disease and potential therapeutic targets in pediatric pulmonary hypertension. We sought to characterize the circulating microRNA profiles of a diverse array of pediatric patients with pulmonary hypertension using high-throughput sequencing technology. Peripheral blood samples were drawn from patients recruited at the time of a clinically indicated cardiac catheterization, and microRNA sequencing followed by differential expression and target/pathway enrichment analyses were performed. Among 63 pediatric patients with pulmonary hypertension, we identified specific microRNA signatures that uniquely classified patients by disease subtype, correlated with indicators of disease severity including invasive hemodynamic metrics, and changed over the course of treatment for pulmonary hypertension. These microRNA profiles include a number of specific microRNA molecules known to function in signaling pathways critical to pulmonary vascular biology and disease, including transforming growth factor-β (TGF-β), VEGF, PI3K/Akt, cGMP-PKG, and HIF-1 signaling. Circulating levels of miR-122-5p, miR-124-3p, miR-204-5p, and miR-9-5p decreased over the course of treatment in a subset of patients who had multiple samples drawn during the study period. Our findings support the further investigation of specific microRNAs as mechanistic mediators, biomarkers, and therapeutic targets in pulmonary hypertension.<b>NEW & NOTEWORTHY</b> We present novel insight into the circulating microRNA profiles of pediatric patients with pulmonary hypertension. Our findings support the utility of microRNAs as both useful biomarkers of disease severity and potential therapeutic targets in pediatric pulmonary hypertension.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H47-H57"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715184","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":"Associations of circulating T-cell subsets with carotid artery stiffness: the multiethnic study of atherosclerosis.","authors":"Theodore M DeConne, Petra Buzkova, Ryan Pewowaruk, Joseph A Delaney, Bruce M Psaty, Russell P Tracy, Margaret F Doyle, Colleen M Sitlani, Alan L Landay, Sally A Huber, Timothy M Hughes, Alain G Bertoni, Adam D Gepner, Jingzhong Ding, Nels C Olson","doi":"10.1152/ajpheart.00649.2024","DOIUrl":"10.1152/ajpheart.00649.2024","url":null,"abstract":"<p><p>Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with an increased risk of multiple age-related diseases. T-PWV can be described by structural (S-PWV) and load-dependent (LD-PWV) arterial stiffening. T-cells have been implicated in arterial remodeling, arterial stiffness, and hypertension in humans and animals; however, it is unknown whether T-cells are risk factors for T-PWV or its components. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV. Peripheral blood T-cells were characterized using flow cytometry, and carotid artery stiffness was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a participant subset of the Multi-Ethnic Study of Atherosclerosis (MESA, <i>n</i> = 1,984). A participant-specific exponential model was used to calculate S-PWV and LD-PWV based on elastic modulus and blood pressure gradients. The associations between five primary (<i>P</i>-significance < 0.01) and 25 exploratory (<i>P</i>-significance < 0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted linear regression models. For the primary analysis, higher CD4⁺CD28^-CD57⁺, but not CD8⁺CD28^-CD57⁺, T-cells were associated with higher LD-PWV (β = 0.04 m/s, <i>P</i> < 0.01) after adjusting for covariates. None of the remaining T-cell subpopulations in the primary analysis were associated with T-PWV or S-PWV. For the exploratory analysis, several memory and differentiated/senescence-associated CD4⁺ and CD8⁺ T-cell subpopulations were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for covariates. In conclusion, we highlight novel associations in humans between CD4⁺ and CD8⁺ memory and differentiated/senescence-associated T-cell subpopulations and measures of arterial stiffness in MESA. These results warrant longitudinal, prospective studies that examine changes in T-cell subpopulations and arterial stiffness in humans.<b>NEW & NOTEWORTHY</b> We investigated associations between T-cells and novel measures of structural and load-dependent arterial stiffness in a large multiethnic cohort. The primary analysis revealed that pro-inflammatory, senescence-associated CD4⁺CD28^-CD57⁺ T-cells were associated with higher load-dependent arterial stiffness. An exploratory analysis revealed that multiple pro-inflammatory CD4⁺ and CD8⁺ T-cell subpopulations were associated with both higher structural and load-dependent arterial stiffness. These results suggest that pro-inflammatory T-cells may contribute to arterial stiffness through both arterial remodeling and elevated blood pressure.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H113-H119"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715171","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":"Reduced microvascular flow-mediated dilation in Syrian hamsters lacking δ-sarcoglycan is caused by increased oxidative stress.","authors":"Alexis Richard, Arnaud Bocquet, Eric Belin de Chantemèle, Kevin Retailleau, Bertrand Toutain, Héloïse Mongue-Din, Anne-Laure Guihot, Céline Fassot, Yves Fromes, Daniel Henrion, Laurent Loufrani","doi":"10.1152/ajpheart.00569.2024","DOIUrl":"10.1152/ajpheart.00569.2024","url":null,"abstract":"<p><p>δ-Sarcoglycan mutation reduces mechanotransduction and induces dilated cardiomyopathy with aging. We hypothesized that in young hamsters with δ-sarcoglycan mutation, which do not show cardiomyopathy, flow mechanotransduction might be affected in resistance arteries as the control of local blood flow. Flow-mediated dilation (FMD) was measured in isolated mesenteric resistance arteries, using 3-mo-old hamsters carrying a mutation in the δ-sarcoglycan gene (CH-147) and their control littermates. The FMD was significantly reduced in the CHF-147 group. Nevertheless, passive arterial diameter, vascular structure, and endothelium-independent dilation to sodium nitroprusside were not modified. Contraction induced by KCl was not modified, whereas contraction due to phenylephrine was increased. The basal nitric oxide production and total endothelial nitric oxide synthase (eNOS) expression levels were not altered. Nevertheless, eNOS phosphorylation, focal adhesion kinases, and RhoA expression were reduced in CH-147. In contrast, p47phox, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, and reactive oxygen species (ROS) levels were higher in the endothelium of CHF-147 hamsters. Reducing ROS levels using the superoxide dismutase analog Tempol significantly restored the flow-mediated dilation (FMD) levels in CHF-147 hamsters. However, treatment with the COX-2 inhibitor NS-398 showed a nonsignificant improvement in FMD.<b>NEW & NOTEWORTHY</b> This study suggests that the sarcoglycan complex is selectively involved in flow-mediated dilation, thus highlighting its role in endothelial responsiveness to shear stress and amplifying tissue damage in myopathy.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H75-H83"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556962","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":"Reduced cofilin activity as a mechanism contributing to endothelial cell stiffening in type 2 diabetes.","authors":"Gavin Power, Olubodun M Lateef, Francisco I Ramirez-Perez, Yoskaly Lazo-Fernandez, Marc A Augenreich, Larissa Ferreira-Santos, Rogerio N Soares, Juan D Gonzalez-Vallejo, Marianna Morales-Quinones, Charles E Norton, Camila Manrique-Acevedo, Luis A Martinez-Lemus, Jaume Padilla","doi":"10.1152/ajpheart.00667.2024","DOIUrl":"10.1152/ajpheart.00667.2024","url":null,"abstract":"<p><p>An emerging instigator of endothelial dysfunction in type 2 diabetes (T2D) is the stiffening of the cell. Previous reports suggest that polymerization of filamentous actin (F-actin) is a potential mediator of endothelial stiffening. Actin polymerization is limited by active cofilin, an F-actin-severing protein that can be oxidized, leading to its inactivation and loss of severing capability. Yet, whether these mechanisms are implicated in endothelial stiffening in T2D remains unknown. Herein, we report that endothelial cells exposed to plasma from male and female subjects with T2D, and the aortic endothelium of diabetic male mice (<i>db/db</i>), exhibit evidence of increased oxidative stress, F-actin, and stiffness. Furthermore, we show reactive oxygen species, including H₂O₂, are increased in the endothelium of mesenteric arteries isolated from <i>db/db</i> male mice, and that exposure of endothelial cells to H₂O₂ induces F-actin formation. We also demonstrate, in vitro, that cofilin-1 can be oxidized by H₂O₂, leading to reduced F-actin severing activity. Finally, we provide evidence that genetic silencing or pharmacological inhibition of LIM kinase 1, an enzyme that phosphorylates and thus inactivates cofilin, reduces F-actin and cell stiffness. In aggregate, this work supports the inactivation of cofilin as a potential novel mechanism underlying endothelial stiffening in T2D.<b>NEW & NOTEWORTHY</b> Cell stiffening is an emerging contributor to endothelial dysfunction, a classic feature of type 2 diabetes (T2D). However, the mechanisms underlying endothelial stiffening remain largely unknown. This work provides evidence that oxidative stress-induced inactivation of cofilin, a key F-actin severing protein, may be implicated in increasing endothelial F-actin and cell stiffness in T2D.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H84-H92"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749520","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":"Impaired maternal central hemodynamics precede the onset of vascular disorders of pregnancy at high altitude.","authors":"Rosalieke E Wiegel, Kori Baker, Carla Calderon-Toledo, Richard Gomez, Sergio Gutiérrez-Cortez, Julie A Houck, Alison Larrea, Litzi Lazo-Vega, Lorna G Moore, Julia Pisc, Lilian Toledo-Jaldin, Colleen G Julian","doi":"10.1152/ajpheart.00520.2024","DOIUrl":"10.1152/ajpheart.00520.2024","url":null,"abstract":"<p><p>Hypertensive disorders of pregnancy represent an escalating global health concern with increasing incidence in low- to middle-income countries and high-income countries alike. The current lack of methods to detect the subclinical stages of preeclampsia (PE) and fetal growth restriction (FGR), two common vascular disorders of pregnancy, limits treatment options to minimize acute- and long-term adverse outcomes for both mother and child. To determine whether impaired maternal cardiovascular or uteroplacental vascular function precedes the onset of PE and/or FGR (PE-FGR), we used noninvasive techniques to obtain serial measurements of maternal cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and uterine and fetal arterial resistance at <i>gestational weeks 10-16</i>, <i>20</i>-<i>24</i>, and <i>30-34</i> for 79 maternal-infant pairs in La Paz-El Alto, Bolivia (3,850 m), where the chronic hypoxia of high altitude increases the incidence of PE and FGR. Compared with controls (<i>n</i> = 55), PE-FGR cases (<i>n</i> = 24) had lower SV, higher SVR, and greater uterine artery resistance at 10-16 wk. In addition, fetuses of women with lower SV and higher SVR at 10-16 wk showed evidence of brain sparing at 30-34 wk and had lower birth weights, respectively. Although the trajectory of SV and SVR across pregnancy was similar between groups, PE-FGR cases had a comparatively blunted rise in CO from the first to the third visit. Impaired maternal central hemodynamics and increased uteroplacental resistance precede PE-FGR onset, highlighting the potential use of such measures for identifying high-risk pregnancies at high altitudes.<b>NEW & NOTEWORTHY</b> In this prospective study of maternal central hemodynamics at high altitude, pregnancies later affected by preeclampsia (PE) and/or fetal growth restriction (FGR) show elevated systemic and uterine vascular resistance and reduced stroke volume as early as 10-16 wk gestation. Maternal hemodynamic assessments could facilitate early detection of high-risk pregnancies, improving resource allocation and reducing adverse outcomes. We propose an integrated model linking maternal cardiovascular performance to placental insufficiency, enhancing the understanding of PE-FGR in high-altitude settings.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H174-H185"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805823","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":"Guidelines for assessing ventricular pressure-volume relationships in rodents.","authors":"Oliver H Wearing, Naomi C Chesler, Mitchel J Colebank, Timothy A Hacker, John N Lorenz, Jeremy A Simpson, Christopher R West","doi":"10.1152/ajpheart.00434.2024","DOIUrl":"10.1152/ajpheart.00434.2024","url":null,"abstract":"<p><p>Ventricular catheterization with a pressure-volume (PV) catheter is the gold-standard method for assessing in vivo cardiac function in animal studies, providing valuable \"load-independent\" indices of systolic and diastolic heart performance. PV studies are commonly performed to elucidate mechanistic insights into cardiovascular disease using surgical and genetically engineered rat and mouse models, but there is considerable heterogeneity in how these studies are performed. Wide variation in protocol design, volume calibration, anesthesia, manipulation of cardiac loading conditions, how load-independent indices of cardiac function are derived, as well as in data analysis and reporting is constraining reliability and reproducibility in the field. The purpose of this manuscript is to combine our collective expertise in performing open- and closed-chest left and right ventricle PV studies in rodents to provide consensus guidelines on how to perform, analyze, and interpret these studies using either conductance or admittance PV catheters. We first review recent methodological reporting in rodent PV studies in this journal and discuss important details required to improve reproducibility within and across PV studies. We then recommend steps to obtain high-quality PV data, from volume calibration to choice of anesthetic agent and acquiring load-independent indices of both systolic and diastolic function. We also consider between- and within-animal variation and recommend how to perform data analysis and visualization. We hope that this consensus paper guides those performing PV studies in rodents and helps align the field with best practices in surgical/analytical methodologies and reporting, facilitating better reliability and reproducibility in the PV field.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H120-H140"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765643","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":"Vasculature of older females shows heterogeneity in the association between cardiovascular risk and vascular function.","authors":"Thiago Silveira Alvares, Vivian Pinheiro, Tatiane Gomes, Juan Manuel Murias, Rogerio Nogueira Soares","doi":"10.1152/ajpheart.00731.2024","DOIUrl":"10.1152/ajpheart.00731.2024","url":null,"abstract":"<p><p>Although affecting both sexes, loss of sex hormones and consequently increased risk for cardiovascular disease (CVD) render particular features to vascular aging in females. More importantly, although the female's vasculature is more sensitive to CVD risk factors, CVD is often underdiagnosed in women. In the present study, we investigated vascular function in the arm and leg skeletal muscle microvasculature and conduit artery in young and older females. We also applied a mixed-effect regression analysis to examine the relationship between vascular function and CVD risk factors in women. We showed that the detrimental effects of age in conduit artery vascular function, as assessed by flow-mediated dilation (%FMD), were more evident in the lower limb (older, 2.6 ± 0.5 vs. young, 7.2 ± 0.9%; <i>P</i> = 0.0116) compared with the upper limb (older, 5.3 ± 0.5 vs. young, 7.3 ± 0.4%; <i>P</i> = 0.175). In addition, we demonstrate that CVD risk factors, mainly plasma lipid levels [very low-density lipoprotein cholesterol (VLDL-c): <i>r</i>² = 0.415, <i>P</i> = 0.007; high-density lipoprotein cholesterol (HDL-c): <i>r</i>² = 0.313, <i>P</i> = 0.024; triglycerides: <i>r</i>² = 0.422, <i>P</i> = 0.006] and insulin sensitivity index [homeostasis model assessment of insulin resistance (HOMA-IR): <i>r</i>² = 0.635, <i>P</i> < 0.001; QUICKI: <i>r</i>² = 0.792, <i>P</i> < 0.001], were exclusively associated with upper limb skeletal muscle microvascular function in older females. In aggregate, our findings provide novel evidence that impairments in conduit artery function in older females are more pronounced in the lower limb vasculature compared with the upper limb. Also, we demonstrate that older women's upper limb microvasculature function may be more susceptible to the impact of CVD risk factors than lower limb microvasculature function and both limb's conduit arteries.<b>NEW & NOTEWORTHY</b> Even though the vasculature of older females has been suggested to be more sensitive to the detrimental effects of traditional cardiovascular risk factors, cardiovascular disease in women is often underdiagnosed. We show that aging-associated vascular dysfunction is more evident in the lower limb conduit arteries compared with the upper limb in older women. More importantly, we demonstrate that traditional cardiovascular risk factors were exclusively associated with upper limb skeletal muscle microvascular function in older females.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H93-H100"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765648","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}