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

{"title":"BRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression.","authors":"Katherine B Schuetze, Matthew S Stratton, Rushita A Bagchi, Alexander R H Hobby, Marina B Felisbino, Marcello Rubino, Lee S Toni, Caroline Reges, Maria A Cavasin, Rachel H McMahan, Michael Alexanian, Ronald J Vagnozzi, Timothy A McKinsey","doi":"10.1152/ajpheart.00438.2024","DOIUrl":"10.1152/ajpheart.00438.2024","url":null,"abstract":"<p><p>Bromodomain and extraterminal domain (BET) proteins, including BRD4, bind acetylated chromatin and coactivate gene transcription. A BET inhibitor, JQ1, prevents and reverses pathological cardiac remodeling in preclinical models of heart failure. However, the underlying cellular mechanisms by which JQ1 improves cardiac structure and function remain poorly defined. Here, we demonstrate that BRD4 knockdown reduced expression of genes encoding CC chemokines in cardiac fibroblasts, suggesting a role for this epigenetic reader in controlling fibroblast-immune cell cross talk. Consistent with this, JQ1 dramatically suppressed recruitment of monocytes to the heart in response to stress. Normal mouse hearts were found to have approximately equivalent numbers of major histocompatibility complex (MHC-II)^high and MHC-II^low resident macrophages, whereas MHC-II^low macrophages predominated following JQ1 treatment. Single-cell RNA-seq data confirmed that JQ1 treatment or BRD4 knockout in CX3CR1⁺ cells reduced MHC-II gene expression in cardiac macrophages, and studies with cultured macrophages further illustrated a cell autonomous role for BET proteins in controlling the MHC-II axis. Bulk RNA-seq analysis demonstrated that JQ1 blocked pro-inflammatory macrophage gene expression through a mechanism that likely involves repression of NF-κB signaling. JQ1 treatment reduced cardiac infarct size in mice subjected to ischemia/reperfusion. Our findings illustrate that BET inhibition affords a powerful pharmacological approach to manipulate monocyte-derived and resident macrophages in the heart. Such an approach has the potential to enhance the reparative phenotype of macrophages to promote wound healing and limit infarct expansion following myocardial ischemia.<b>NEW & NOTEWORTHY</b> BRD4 inhibition blocks stress-induced recruitment of pro-inflammatory monocytes to the heart. BRD4 inhibition reprograms resident cardiac macrophages toward a reparative phenotype marked by reduced NF-κB signaling and diminished MHC-II expression. BRD4 inhibition reduces infarct size in an acute model of ischemia/reperfusion injury in mice.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H294-H309"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880879","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":"A comment on the physiological basis for longitudinal motion of the arterial wall.","authors":"Magnus Cinthio, Artturi Petäjä, Tobias Erlöv, Åsa Rydén Ahlgren","doi":"10.1152/ajpheart.00597.2024","DOIUrl":"10.1152/ajpheart.00597.2024","url":null,"abstract":"<p><p>The longitudinal motion and the intramural shear strain of the arterial wall increase dramatically in response to blood pressure, thereby impacting the vascular wall microenvironment. Exposure to a sedentary lifestyle has been identified as an independent risk factor for cardiovascular disease, but it has been shown that intermittent physical activity embedded into everyday life is enough to improve cardiovascular health. Marked changes in longitudinal motion already at a low workload may explain this finding. However, to understand the mechanism linking longitudinal motion and cardiovascular health, an understanding of the physiological basis for the longitudinal motion of the arterial wall is needed. The factors underlying the longitudinal motion of the arterial wall in vivo are numerous and intertwined. As a comment and complement to the recent review by Athaide et al. (<i>Am J Physiol Heart Circ Physiol</i> 322: H689-H701, 2022), we propose and discuss a comprehensive cardiovascular mechanical scenario based on the current literature. In this scenario, blood pressure, typically acting in the radial direction, also acts directly in the longitudinal direction through a tapered geometry. This complements ventricular contraction, ventricular-vascular coupling, arterial diameter change, arterial stiffness in both the radial and longitudinal directions, and prestretch of the arterial wall. In addition, we consider the geometry of the arterial tree and intramural friction of the arterial wall. Together, these important cardiovascular mechanical factors form the pattern of longitudinal motion of the arterial wall, indicating that the longitudinal motion of the arterial wall is important for cardiovascular health.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H190-H195"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871056","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 6-min walk test: improving the prognostic power.","authors":"Karen L Ball","doi":"10.1152/ajpheart.00846.2024","DOIUrl":"10.1152/ajpheart.00846.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H187-H189"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871059","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 impact of oral contraceptive pill use on sympathetic transduction at rest in young females.","authors":"Andrew W D'Souza, Sarah L Hissen, Kazumasa Manabe, Takuro Washio, Meghan C Annis, Belinda Sanchez, Charlotte W Usselman, Qi Fu, J Kevin Shoemaker","doi":"10.1152/ajpheart.00623.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00623.2024","url":null,"abstract":"<p><p>Although previous work has demonstrated that oral contraceptive pill (OCP) use does not affect resting muscle sympathetic nerve activity (MSNA), growing evidence indicates that it attenuates neurogenic vasoconstriction. Despite these advances, it remains unknown how OCP use affects the ability of MSNA to dynamically control vascular tone and arterial blood pressure (BP) on a beat-by-beat basis. Thus, we tested the hypothesis that, compared with naturally menstruating females (MC), those using OCPs will exhibit attenuated sympathetic vascular transduction at rest. Forty-three females [MC: <i>n</i> = 21, 26 (4) yrs; OCP: <i>n</i> = 22, 24 (4) yrs; data are presented as means (SD)] completed 10 min of supine rest with continuous measurements of beat-by-beat BP, femoral artery blood flow (26 females; MC: <i>n</i> = 13, OCP: <i>n</i> = 13), and MSNA. Spike-triggered averaging was used to determine sympathetic transduction into leg vascular conductance (LVC) and BP for 12 cardiac cycles following MSNA bursts. Overall sympathetic-BP transduction (<i>P</i> = 0.293), as well as sympathetic-BP transduction of MSNA burst quartiles (<i>P</i> = 0.741) and burst firing patterns (<i>P</i> = 0.452) were not different between the MC and OCP groups. Conversely, sympathetic vascular transduction per unit MSNA burst amplitude (<i>P</i> = 0.026) and burst firing pattern (<i>P</i> = 0.014) were attenuated among females using OCPs. In addition, females using OCPs demonstrated progressively smaller leg vasoconstrictor responses as a function of MSNA burst firing pattern compared with MC females (<i>P</i> = 0.021). Collectively, these data indicate that, in premenopausal females, OCP use attenuates the leg vasoconstrictor responses to bursts of MSNA, particularly during periods of increased sympathetic neural drive, without affecting the transduction of MSNA bursts into beat-by-beat changes in BP.<b>NEW & NOTEWORTHY</b> This study investigated the impact of OCP use on the transduction of MSNA bursts into regional vasoconstriction and blood pressure in premenopausal females. We demonstrated that females using OCPs exhibit attenuated sympathetic transduction into LVC; however, this does not translate to reductions in sympathetic blood pressure transduction. Collectively, these data indicate that OCP use may alter the local vasoconstrictor response to bursts of MSNA; however, compensatory mechanisms may contribute to maintain sympathetic blood pressure transduction.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 2","pages":"H271-H282"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998699","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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901338/pdf/","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":"OA","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}