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

{"title":"Unraveling the NO-sGC-cGMP pathway in BPD-associated pulmonary hypertension.","authors":"Kimra S James, My N Helms","doi":"10.1152/ajpheart.90017.2026","DOIUrl":"10.1152/ajpheart.90017.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1338-H1340"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904837","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":"Sex-dependent epigenomic and transcriptomic reprogramming links maternal obesity to cardiac remodeling in adult offspring.","authors":"Tim D Wilson, Elysse A Phillips, Yem J Alharithi, Cameron Broberg, Joshua Vanderpool, Shauna Rakshe, Suzanne S Fei, Brett A Davis, Sheryl Koch, Zhehao Zhu, Lyndsey E Shorey-Kendrick, Sushil Kumar, Lucia Carbone, Yabing Chen, Jamie O Lo, Jack Rubinstein, Susan B Gurley, Karina H Nakayama, Sandra Rugonyi, Alina Maloyan","doi":"10.1152/ajpheart.00507.2026","DOIUrl":"10.1152/ajpheart.00507.2026","url":null,"abstract":"<p><p>Maternal obesity during pregnancy predisposes the offspring to a high risk of developing cardiovascular and metabolic diseases later in life. This study investigated cardiac perturbations caused by maternal obesity by utilizing a mouse model of maternal high-fat diet (HFD)-induced obesity that recapitulates metabolic abnormalities observed in humans. Our study revealed that offspring of HFD-fed mothers (Off-HFD) exhibit a progression of obesity, dyslipidemia, and metabolic inflexibility when compared with offspring of regular diet-fed mothers (Off-RD). Deeper investigation of cardiac function revealed profound functional, metabolic, vascular, and immune perturbations in adult Off-HFD mice, with marked sex-specific differences. Although both male and female Off-HFD mice developed progressive cardiac hypertrophy, male offspring exhibited a more severe phenotype characterized by hypertension, increased vascular stiffness, cardiac dysfunction, and fibrosis. To identify potential mechanisms underlying these changes, we performed DNA methylation analysis in collected hearts of newly weaned and adult offspring. This analysis revealed extensive, sex-dependent alterations in DNA methylation within or nearby genes involved in cardiac development, lipid metabolism, hypertrophic growth, and inflammatory signaling. Importantly, many of these epigenetic alterations persisted into adulthood, suggesting that maternal obesity establishes a durable molecular memory in the offspring heart. Consistent with these findings, transcriptome analysis of adult hearts revealed activation of gene programs associated with heart failure and pathological cardiac remodeling in male Off-HFD mice, whereas female Off-HFD mice showed activation of pathways consistent with adaptive or cardioprotective responses. Together, these findings demonstrate that maternal HFD induces early-life epigenetic remodeling in the offspring heart that persists into adulthood and is associated with sex-specific metabolic, functional, vascular, and immune dysregulation. By linking early epigenomic changes to adult cardiac disease susceptibility, this study identifies potential developmental windows for preventive and early therapeutic interventions aimed at reducing cardiovascular risk in offspring exposed to maternal obesity in utero.<b>NEW & NOTEWORTHY</b> This study identifies persistent, sex-dependent epigenomic and transcriptional remodeling as a potential mechanism linking maternal obesity to cardiovascular disease susceptibility in offspring. Integrating longitudinal cardiometabolic phenotyping with cardiac DNA methylation and transcriptomic analyses, we demonstrate that a maternal high-fat diet induces early-life molecular alterations that persist into adulthood and are associated with cardiac hypertrophy, fibrosis, vascular stiffening, and functional impairment. These findings support the concept of a lasting developmental molecular memory in the heart that may underlie sex-specific cardi","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1307-H1328"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910639","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":"Excessive hypercholesterolemia in pregnancy alters maternal cardiac remodeling during pregnancy and postpartum.","authors":"Amanda A de Oliveira, Raven Kirschenman, Kelli Hsiao, Anita Quon, Murilo E Graton, Christy-Lynn M Cooke, Sandra T Davidge","doi":"10.1152/ajpheart.00456.2026","DOIUrl":"10.1152/ajpheart.00456.2026","url":null,"abstract":"<p><p>Excessive hypercholesterolemia (eHC) in pregnancy is associated with complications such as preeclampsia, yet its impact on maternal cardiac adaptation and long-term cardiovascular health remains unclear. We hypothesized that eHC impairs maternal cardiac structure and function during pregnancy and that these effects persist postpartum. Sprague Dawley rats were fed either a control diet (CTL) or high-cholesterol diet (eHC) from <i>gestational day</i> (GD) <i>6</i>-<i>20</i> (term = 22 days). Echocardiography was performed before pregnancy, at GD20, and 3 mo postpartum. Plasma and left ventricular tissue were collected at GD20 and postpartum for molecular analyses. CTL dams demonstrated normal pregnancy-associated cardiac adaptations, including increased diastolic left ventricular internal diameter, stroke volume, cardiac output, and diastolic left ventricular volume in late pregnancy, with normalization postpartum. These adaptations were attenuated in eHC dams. In late pregnancy, eHC dams exhibited reduced stroke volume and cardiac output compared with CTL, along with alterations in diastolic function, including reduced mitral valve A' velocity. Postpartum, eHC dams showed changes in diastolic indices, including reduced mitral valve A-wave velocity and E'/A' ratio. Measures of systolic performance (ejection fraction and fractional shortening) were unchanged between groups. Molecular analyses revealed increased cardiomyocyte size, altered collagen remodeling characterized by an increased type I collagen (COL1)-to-type I collagen 3 (COL3) ratio, and elevated CD31 expression in eHC dams during pregnancy. Postpartum, collagen remodeling was evident, but now with reduced COL1 and increased COL3 expression. Together, these findings demonstrate that eHC disrupts normal maternal cardiac adaptation during pregnancy and promotes adverse remodeling and cardiac dysfunction postpartum, with potential implications for long-term cardiovascular disease risk.<b>NEW & NOTEWORTHY</b> Excessive hypercholesterolemia impairs the adaptive cardiac remodeling normally associated with pregnancy and postpartum recovery, indicating reduced cardiac plasticity. Although systolic function remained preserved, altered hemodynamic responses, diastolic parameters, and tissue markers indicate early subclinical maladaptive remodeling. These findings suggest that excessive hypercholesterolemia compromises the maternal heart's ability to accommodate the physiological demands of pregnancy.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1172-H1181"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878711","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":"An IDeA for increasing biomedical research capacity.","authors":"Lawrence E Cornett, Francis G Spinale, Edie C Goldsmith","doi":"10.1152/ajpheart.00618.2026","DOIUrl":"10.1152/ajpheart.00618.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1090-H1092"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811822","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":"Absence of directional sensitivity of dynamic cerebral autoregulation in acute ischemic stroke.","authors":"Jonathan Ince, Ronney B Panerai, Angela S M Salinet, Man Y Lam, Osian Llwyd, Victoria J Haunton, Thompson G Robinson, Jatinder S Minhas","doi":"10.1152/ajpheart.00546.2026","DOIUrl":"10.1152/ajpheart.00546.2026","url":null,"abstract":"<p><p>Dynamic cerebral autoregulation (dCA) is impaired in acute ischemic stroke (AIS) and this dysfunction has been associated with worse clinical outcomes. It has been demonstrated that the cerebral circulation responds differently to increases and decreases of mean arterial blood pressure (MAP). This phenomenon is known as directional sensitivity and has been characterized in healthy participants but is yet to be described in AIS. We hypothesize that directional sensitivity is impaired following AIS and may contribute to the altered dCA seen in stroke. Retrospective analysis of transcranial Doppler ultrasound recordings of middle cerebral artery blood velocity were analyzed in 34 patients with AIS (23 males) and 34 age-matched healthy controls (22 males). Following correction for differences in EtCO₂, directional sensitivity was observed in controls, but absent in patients with AIS. For example, median autoregulatory index measures during increases (ARI_+D) and decreases (ARI_-D) in MAP were impaired following AIS (affected hemisphere: ARI_+D 5.3 [IQR: 3.7, 6.3], ARI_-D 4.4 [IQR: 3.8, 6.1], <i>P</i> = 0.088; unaffected hemisphere: ARI_+D 5.3 [IQR: 4.1, 6.1], ARI_-D 4.2 [3.5, 6.1], <i>P</i> = 0.174) compared with control (right hemisphere: ARI_+D 6.6 [IQR: 5.3, 8.2], ARI_-D 5.7 [IQR: 3.6, 5.4], <i>P</i> = 0.007; left hemisphere: ARI_+D 6.4 [IQR: 5.0, 8.2], ARI_-D 5.5 [4.6, 6.9], <i>P</i> = 0.026). As AIS was associated with impaired responses to increases and decreases in MAP, dysfunction of vasoconstriction and vasodilation are suspected. These changes may relate to the effect of AIS on the endothelium, vascular smooth muscle, or piezo mechanosensitive ion channels.<b>NEW & NOTEWORTHY</b> Patients with AIS demonstrate significantly impaired dynamic cerebral autoregulation compared with controls. AIS was associated with lower autoregulation index parameters and absent directional sensitivity of the cerebral pressure-flow relationship. We speculate that these results are due to AIS-induced impairment to both cerebral vasoconstriction and vasodilation mechanisms.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1329-H1337"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944110","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":"Validation of the detection of the salt sensitivity of blood pressure from 24-h ambulatory blood pressure monitoring data.","authors":"Xiangyu Zheng, Leonardo Máximo Cardoso, Christopher Dieffenthaller, Arshed A Quyyumi, Puja K Mehta, Richard D Wainford","doi":"10.1152/ajpheart.00460.2026","DOIUrl":"10.1152/ajpheart.00460.2026","url":null,"abstract":"<p><p>The salt sensitivity of blood pressure (SSBP) is rarely assessed and represents a critical barrier in precision hypertension treatment. The current approaches to assess salt sensitivity are labor- and resource-intensive, limiting their clinical implementation. The salt sensitivity index (SSI), derived from 24-h ambulatory blood pressure monitoring (ABPM) data, has been proposed as a clinical diagnostic approach to classify individuals at low-, intermediate-, or high-risk for SSBP. This study utilized the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial control diet arm dataset (<i>n</i> = 170), in which SSBP was assessed by the gold-standard dietary approach, to address the hypothesis that identification of a high-risk SSI can predict the individual SSBP. In the high-risk SSI category, 72% of participants exhibited a salt-sensitive phenotype. For all participants with a high-risk SSI (male and female and normotensive and hypertensive), sensitivity (ability to correctly identify individuals with SSBP) was 85%, specificity (ability to correctly identify individuals without SSBP) was 41%, positive predictive value (probability that a person who tests positive has SSBP) was 72%, negative predictive value (probability that a person who tests negative does not have SSBP) was 60%, and accuracy was 69%. For hypertensive participants only with a high-risk SSI (males and females), sensitivity was 86%, specificity was 44%, the positive predictive value increased to 83%, the negative predictive value was 50%, and accuracy increased to 76%. This study validates the identification of a high-risk SSI, based on 24-h ABPM, as a generalizable, implementable approach for the clinical diagnosis of SSBP, with potentially greater clinical diagnostic value in hypertensive versus normotensive individuals.<b>NEW & NOTEWORTHY</b> This study, conducted in the DASH-Sodium dataset, validates the identification of a high-risk salt sensitivity index, based on 24-h ambulatory blood pressure monitoring, as a generalizable, easily implementable approach for the clinical diagnosis of the salt sensitivity of blood pressure. As this approach possesses greater sensitivity and comparable accuracy to the furosemide-based inpatient protocol, we believe that the assessment of the salt sensitivity index in hypertensive patients represents an advance in precision hypertension management.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1037-H1043"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787217","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":"Sympathetic vascular transduction in adults with hypertension and obesity-associated hypertension.","authors":"Giorgio Manferdelli, Sarah L Hissen, Denis J Wakeham, Auvin Oghatiyan, Scott L Davis, Satyam Sarma, Benjamin D Levine, Paul J Fadel, Christopher M Hearon","doi":"10.1152/ajpheart.00298.2026","DOIUrl":"10.1152/ajpheart.00298.2026","url":null,"abstract":"<p><p>Half of adult Americans have high resting blood pressure (BP). Although elevated muscle sympathetic nerve activity (MSNA) is a common characteristic of essential hypertension, resting sympathetic activation is highly variable. This variability may relate to alterations in the transduction of MSNA to vasoconstriction. It is unknown whether sympathetic vascular transduction is altered in hypertension, or how obesity, a common comorbidity, modifies vascular transduction. Sympathetic transduction was quantified in 12 normotensive [CON; age: 38 ± 10 yr, body mass index (BMI): 25 ± 3 kg·m^-2] and 30 hypertensive adults [12 nonobese (N-HTN): age: 44 ± 6 yr, BMI: 27 ± 3 kg·m^-2; and 18 with obesity (OB-HTN): age: 40 ± 10 yr, BMI: 38 ± 5 kg·m^-2]. Continuous measurements of MSNA (microneurography), mean arterial pressure (MAP, photoplethysmography), and superficial femoral artery blood flow (LBF, Doppler ultrasound) were used to calculate beat-by-beat leg vascular conductance (LVC; LBF/MAP). Transduction to LVC and MAP was quantified using signal averaging and compared using a mixed-effects model with age, sex, race, and menopausal status as covariates. MSNA burst frequency (<i>P</i> = 0.255) and incidence (<i>P</i> = 0.417) were not different between groups. Sympathetic vascular transduction to multiple MSNA bursts was blunted in N-HTN (group: <i>P</i> = 0.029), leading to a slower BP response compared to CON (interaction: <i>P</i> = 0.030). The downregulation of sympathetic vascular transduction was less apparent in OB-HTN and associated with higher sympathetic transduction to diastolic BP compared to N-HTN (<i>P</i> = 0.041). Compared to CON, sympathetic vascular transduction was attenuated in N-HTN but remained relatively preserved in OB-HTN. These data indicate that OB-HTN may be characterized by a greater contribution of sympathetic vascular transduction to blood pressure regulation.<b>NEW & NOTEWORTHY</b> Sympathetic vascular transduction is blunted in hypertensive adults relative to normotensive adults, which is in line with compensatory downregulation of vascular transduction to offset elevated sympathetic vasomotor outflow. The compensatory downregulation of sympathetic vascular transduction is less apparent in obesity-associated hypertension, despite no detectable difference in transduction to blood pressure between groups. Our data provide insight regarding differential sympathetic-vascular mechanisms of blood pressure control in adults with hypertension and obesity-associated hypertension.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1380-H1389"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023482","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 transient gestational insult with lasting cardiovascular consequences: modeling maternal risk after gestational diabetes.","authors":"Oh Sung Kwon, Eunhee Chung","doi":"10.1152/ajpheart.90156.2026","DOIUrl":"10.1152/ajpheart.90156.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1214-H1216"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954649","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":"Predominant α₂-adrenoceptor control of chelonian systemic resistance arteries provides a mechanistic basis for the cardiovascular effects of α₂-agonist sedation.","authors":"Asbjørn Onsberg Kruuse, Rasmus Wibrand, Samuel N Baldwin, Tobias Wang, Mads Frost Bertelsen, Thomas A Jepps","doi":"10.1152/ajpheart.00563.2026","DOIUrl":"10.1152/ajpheart.00563.2026","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Chelonians are commonly sedated with α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor agonists, such as medetomidine, and bradycardia is consistently reported following administration. This may reflect a baroreflex response to α&lt;sub&gt;2&lt;/sub&gt;-mediated peripheral vasoconstriction and increased systemic vascular resistance, but the vascular contribution to these cardiovascular effects has not been directly investigated. Here, we tested the hypothesis that α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptors contribute predominantly to vascular contraction in chelonians, contrasting with the α&lt;sub&gt;1&lt;/sub&gt;-adrenoceptor-dominant regulation described in mammals. Mesenteric resistance arteries from three chelonian species spanning two chelonian families (&lt;i&gt;Stigmochelys pardalis&lt;/i&gt;, &lt;i&gt;Mauremys reevesii&lt;/i&gt;, and &lt;i&gt;Mauremys sinensis&lt;/i&gt;) were studied using wire myography. Concentration-response curves were generated for the nonselective α-adrenoceptor agonist noradrenaline, the selective α&lt;sub&gt;1&lt;/sub&gt;-adrenoceptor agonist methoxamine, and the α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor agonists medetomidine, detomidine, xylazine, and romifidine. The effects of α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor antagonism with vatinoxan and α&lt;sub&gt;1&lt;/sub&gt;-adrenoceptor antagonism with prazosin were also assessed. Medetomidine and detomidine produced robust, concentration-dependent vasoconstriction, whereas xylazine and romifidine produced weak or inconsistent responses. Vatinoxan attenuated α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor agonist-induced responses, although the magnitude and nature of antagonism differed between species and experimental conditions. Noradrenaline-induced contraction was also attenuated by vatinoxan, whereas methoxamine produced little or no contraction and prazosin had minimal effects on noradrenaline responses. These findings support a predominant functional contribution of α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptors to vascular contraction in the chelonian systemic arteries studied, with comparatively little detectable contribution from α&lt;sub&gt;1&lt;/sub&gt;-adrenoceptors. This adrenergic organization differs from the α&lt;sub&gt;1&lt;/sub&gt;-dominant vascular regulation typical of mammals and identifies chelonian arteries as a useful comparative model for α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor-mediated vascular control. The findings also provide a mechanistic basis for the peripheral vascular component of the cardiovascular response to α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor agonist sedation in chelonians.&lt;b&gt;NEW & NOTEWORTHY&lt;/b&gt; Chelonian systemic arteries exhibit predominantly α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor-mediated contraction, with minimal functional contribution from α&lt;sub&gt;1&lt;/sub&gt;-adrenoceptors, contrasting with mammalian vascular regulation. Medetomidine and detomidine induce robust vasoconstriction that is abolished by the peripherally acting α&lt;sub&gt;2&lt;/sub&gt;-adrenoceptor antagonist vatinoxan. These findings identify a distinct adrenergic hierarchy in chelonian vasculature, provide a mechanistic basis for the cardiovascular effects of α&lt;sub&gt;2&lt;/sub&gt;-agonist sedation, and establish che","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1242-H1251"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904870","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 CD4⁺ T cell response to apolipoprotein B-100 peptide P210 in atherosclerotic cardiovascular disease is reversed by P210-conjugated nanoparticles.","authors":"Paul C Dimayuga, Jianchang Zhou, Xiaoning Zhao, Janet Wei, Noah Trac, Karla Lambaren, Eun Ji Chung, Bojan Cercek, Prediman K Shah, Kuang-Yuh Chyu","doi":"10.1152/ajpheart.00406.2026","DOIUrl":"10.1152/ajpheart.00406.2026","url":null,"abstract":"<p><p>The apolipoprotein B-100 (ApoB-100) peptide P210 (amino acids 3136-3155) is localized within atherosclerotic plaques, and low IgG autoantibody levels against P210 are associated with a higher risk of plaque rupture and myocardial infarction (MI), suggesting that this humoral immunity is protective in atherosclerotic cardiovascular disease (ASCVD). Although the clinical significance of P210 antibody response has been shown, it remains unclear whether patients with ASCVD also exhibit an impaired T cell response to P210. Thus, we investigated the T cell response to P210 in patients with ASCVD and evaluated its potential as a target for therapeutic intervention. Peripheral blood mononuclear cells (PBMCs) collected from patients with ASCVD and controls were stimulated with the P210 peptide and evaluated for T cell responses using the activated immune markers (AIM) assay. PBMCs from patients with ASCVD stimulated with P210 had a significantly impaired CD4⁺CD69⁺CD154⁺ T cell response, which persisted into follow-up a year later. Significantly reduced CD4⁺ T follicular helper cell responses to P210 were also noted in patients with ASCVD. Given the beneficial immunomodulation by P210 nanoparticles (P210-PAM) that resulted in reduced atherosclerosis in mice, we investigated its effect on PBMCs from patients with ASCVD. Treatment with P210-PAM significantly improved the impaired CD4⁺CD69⁺CD154⁺ and CD4⁺CD134⁺CD137⁺ T cell activation in response to P210. The study suggests potential future clinical translation for P210-PAM as an immune-modulation strategy for ASCVD.<b>NEW & NOTEWORTHY</b> Patients with ASCVD have reduced levels of IgG reactive with the apoB-100 peptide P210. Although suggestive of immune suppression specific to P210, it is unclear whether this involves T cell responses as well. The current report demonstrates reduced T cell response to P210 in patients with ASCVD that is reversed by P210-conjugated nanoparticles.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1182-H1190"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787117","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}