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

{"title":"Beyond the traditional paradigm: a unified functional definition and five-axis matrix classification of endothelial dysfunction.","authors":"Andrii Chornomydz, Oleksandra Oleshchuk","doi":"10.1152/ajpheart.90098.2026","DOIUrl":"10.1152/ajpheart.90098.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1217-H1228"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904900","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":"Selective pharmacological blockade of GPR39 markedly reduces no-reflow and infarct volumes in rat acute myocardial infarction when administered before reperfusion.","authors":"Carmen Methner, Mary Plascencia, Allura Thompson, Lijuan Liu, Masaki Kajimoto, D Elizabeth Le, Agostino Cianciulli, Annalisa Pellacani, Jessica Franchi, Chiara Marcheselli, Alberto Parazzoli, Fabrizio Micheli, Sanjiv Kaul","doi":"10.1152/ajpheart.01008.2025","DOIUrl":"10.1152/ajpheart.01008.2025","url":null,"abstract":"<p><p>Our aim was to determine whether selective pharmacological blockade of G protein-coupled receptor 39 (GPR39) by the novel drug, VC108, reduces no-reflow (NRV) and infarct (INV) volumes during acute myocardial infarction (AMI). Immunocytochemistry and quantitative polymerase chain reaction (qPCR) of isolated rat cardiac cells as well as immunohistochemistry and Western blot of rat myocardium were performed for presence of GPR39. Rats underwent 1 h of coronary occlusion and 1 h of reperfusion. <i>Groups 1</i> and <i>2</i> animals received drug/vehicle before or during coronary occlusion. <i>Groups 3</i> and <i>4</i> received drug/vehicle 5 min before or 30 min after reperfusion. Readouts also included tissue Po₂, hemodynamics, and wall thickening. In <i>groups 5</i> and <i>6</i> animals, drug was injected for measurement of plasma and tissue levels. Immunocytochemistry and qPCR of cells and immunohistochemistry and Western blot of tissue revealed GPR39 expression in all cardiac cells analyzed as well as entire myocardial tissue. There was a marked reduction in NRV and INV in <i>groups 1</i> and <i>3</i> animals where both were measured and in <i>group 2</i> where INV was measured. In contrast, <i>group 4</i> animals failed to show a reduction in NRV and INV with the drug. The reduction in NRV in all animals was associated with higher tissue Po₂ in VC108-treated compared with vehicle-treated animals. Similar results were obtained for INV in <i>group 2</i> animals. In <i>group 3</i> animals, a direct cardiomyocyte effect of VC108 was seen in the myocardium as evidenced by reduced necrosis and apoptosis. We conclude that VC108 is very effective in reducing INV and NRV in an AMI model when given before coronary occlusion or just before reperfusion (the latter being clinically more relevant) in both male and female rats. This effect is not seen after reperfusion. VC108 acts by blocking GPR39, resulting in vasodilation through pericyte and vascular smooth muscle cell (VSMC) relaxation. It also directly protects cardiomyocytes by preventing downstream effects of GPR39 stimulation.<b>NEW & NOTEWORTHY</b> GPR39 is the receptor for 15-HETE, which is a vasoconstrictor with direct cardiomyocyte detrimental effects. Pharmacological inhibition of GPR39 by a novel inhibitor, VC108, reduces coronary no-reflow after acute myocardial infarction by relaxing contracted pericytes surrounding capillaries, whereby increasing oxygen delivery. GPR39 inhibition also reduces necrosis and apoptosis by interrupting aberrant downstream signaling responsible for cell death. Hence, pharmacological inhibition of GPR39 by VC108 offers a novel treatment of acute myocardial infarction.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1044-H1065"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787063","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":"Optimized cardiac leukocyte isolation for flow cytometry enumeration and sorting.","authors":"Ayodeji A Olabiyi, Sirin N Cakir, Miki Kassai, Srinivas Sriramula, Leslie M Kennedy, Akshaya K Meher, Debajit Bhowmick, Lisandra E de Castro Braz","doi":"10.1152/ajpheart.00137.2026","DOIUrl":"10.1152/ajpheart.00137.2026","url":null,"abstract":"<p><p>Accurate characterization of immune cell populations within the heart is critical for understanding inflammatory mechanisms that drive cardiac injury and repair. However, isolating viable leukocytes from cardiac tissue remains technically challenging due to the dense extracellular matrix, high collagen content, and susceptibility of immune subsets to enzymatic or mechanical stress. Here, we describe an optimized protocol for cardiac leukocyte isolation that maximizes cell yield, preserves viability, and maintains the integrity of surface markers for flow cytometric analysis and cell sorting. The method integrates controlled enzymatic digestion, gentle mechanical dissociation, and precise debris removal, thereby minimizing stromal contamination and reducing cellular activation artifacts. Using this approach, we demonstrate reproducible recovery of diverse immune populations, including neutrophils, monocytes, macrophages, and lymphocyte subsets from murine hearts. Furthermore, compatibility with high-dimensional flow cytometry and fluorescence-activated cell sorting enables robust downstream applications such as transcriptomic profiling and functional assays. This optimized isolation strategy provides a reliable and versatile tool for investigating the cardiac immune landscape, offering new opportunities to delineate the immunopathology of cardiovascular disease and to develop targeted immunomodulatory therapies.<b>NEW & NOTEWORTHY</b> Flow cytometry of immune cells is highly tissue-specific, requiring tailored enzymatic digestion and staining protocols. We optimized a protocol for cardiac immune cells isolation and enumeration using the following steps: <i>1</i>) tissue digestion, <i>2</i>) cell viability, <i>3</i>) titration of live/dead dye, <i>4</i>) antibody titration, and <i>5</i>) compensation and blocking. The resulting protocol was used both for flow cytometry and FACS analysis of neutrophils, monocytes, and macrophages, but it could easily be extended to innate immune cells.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1433-H1446"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910688","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":"Cardiovascular effects of chronic GIPR and GLP-1R agonism in lean and diet-induced obese mice: sex differences and dose-dependent remodeling.","authors":"Sevilay Şahoğlu Göktaş, Annelise Francisco, João M N Duarte, Anja Meissner, Martin Magnusson","doi":"10.1152/ajpheart.00204.2026","DOIUrl":"10.1152/ajpheart.00204.2026","url":null,"abstract":"<p><p>Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) regulate metabolism and are increasingly targeted in therapies for type 2 diabetes and obesity. Although GLP-1 receptor agonists confer cardiovascular benefits, the cardiovascular effects of GIP receptor (GIPR) stimulation remain controversial. This study aimed at defining the short-term cardiovascular consequences of GIPR and GLP-1 receptor (GLP-1R) agonism in lean and diet-induced obese mice, with emphasis on sex-specific cardiac remodeling patterns. Male and female mice received continuous infusion of a GIPR or GLP-1R agonist for 1 mo at 0.1, 0.4, 0.8, and 1.0 mg/kg/day under chow feeding or an effective dose of 0.8 mg/kg/day after 2 mo of high-fat diet (HFD)-induced obesity. Cardiovascular phenotyping included tail-cuff blood pressure, cardiac magnetic resonance imaging, metabolic testing, and assessment of plasma biomarkers of cardiac stress (ST2 or NT-proBNP). In lean mice, GIPR agonism dose-dependently increased end-diastolic volume, whereas GLP-1R agonism increased end-diastolic left-ventricular (LV) mass in male mice, resulting in divergent remodeling patterns without affecting systolic function. These structural changes occurred without alterations in ST2 or NT-proBNP, suggesting remodeling in the absence of overt myocardial stress. In obese mice, both agonists lowered mean arterial pressure and improved systolic function. GIPR agonism primarily increased LV volume in males, whereas GLP-1R agonism increased LV mass in females. Although ST2 levels were largely driven by HFD, NT-proBNP was reduced by both treatments, consistent with improved cardiac loading conditions. In conclusion, short-term incretin receptor agonism induces distinct, context-dependent cardiovascular remodeling patterns that depended on receptor specificity, metabolic state, and sex. Although both GIPR and GLP-1R agonists exerted beneficial hemodynamic and functional effects in obesity, GIPR stimulation in lean mice increased ventricular volume and GLP-1R stimulation increases mass without overt functional deterioration. These findings demonstrate distinct cardiac actions of incretin pathways and highlight the importance of metabolic context in their therapeutic effects.<b>NEW & NOTEWORTHY</b> Incretin-based therapies are reshaping metabolic disease care, yet the chronic cardiac effects of GIPR agonism remain uncertain. Using comprehensive cardiovascular phenotyping in lean and obese mice, we show that GIPR and GLP-1R agonists drive distinct, sex-dependent patterns of cardiac remodeling despite similarly improving hemodynamics in obesity. GIPR agonism primarily increased LV volume, whereas GLP-1R agonism increased LV mass. These receptor-specific adaptations clarify divergent cardiac responses to incretin therapies and inform evaluation of emerging dual-agonist treatments.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1390-H1401"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962828","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":"Age-associated patterns of cardiovascular risk and disease phenotypes across diverse care settings: the GLOB-cAGE consortium.","authors":"Enyu Yang, Jie Sun, Yanhong Dong, Carlin Chang, Liang Zhong, Gary Tse, Bernard Man Yung Cheung, Sebastián Garcia-Zamora, Angela S Koh","doi":"10.1152/ajpheart.00450.2026","DOIUrl":"10.1152/ajpheart.00450.2026","url":null,"abstract":"<p><p>Reported prevalence of cardiovascular disease (CVD) risk factors and phenotypes varies widely. In multicohort analyses, such variation reflects population risk, care setting, and data capture. We harmonized baseline data from four analytic cohorts (<i>N</i> = 54,188, aged ≥50 yr) in five Global Cardiovascular Collaborative Network of Older Adults with Cardiovascular Disease member studies: pooled community (<i>n</i> = 956), primary care (<i>n</i> = 49,849), acute CVD registry (<i>n</i> = 2,723), and chronic CVD cohort (<i>n</i> = 660). Any risk factor was hypertension, diabetes, or dyslipidemia. Any CVD phenotype was ischemic heart disease, heart failure, or atrial fibrillation/flutter. At age 60-74 yr, any risk-factor prevalence ranged from 10.4% in primary care to 91.4% in the acute CVD registry (<i>P</i> < 0.001); any CVD phenotype prevalence ranged from 4.4% to 47.0% (<i>P</i> < 0.001). In the pooled community cohort, any risk-factor prevalence increased from 28.9% at age 50-59 yr to 85.0% at ≥75 yr (adjacent <i>q</i> < 0.001), whereas age-sex-standardized any CVD phenotype prevalence remained comparatively low (10.6%). Any CVD phenotype prevalence increased with risk-factor-count, with the clearest gradients in the acute CVD registry (35.8%-64.2%; <i>P</i> for trend < 0.001) and pooled community cohort (6.4%-19.6%; <i>P</i> for trend < 0.001). Among participants with any CVD phenotype, female age distributions were older than male distributions in primary care and the acute CVD registry (female-minus-male median age difference, +3.7 and +5.0 yr; both <i>P</i> < 0.001). Across diverse care settings, harmonized summary constructs identified interpretable patterns in cardiovascular risk and CVD burden. These real-world data support cardiovascular prevention across aging, highlight substantial CVD burden among women at older ages, and provide a framework for longitudinal analyses across real-world cohorts.<b>NEW & NOTEWORTHY</b> Using harmonized data from 54,188 older adults in GLOB-cAGE, this study shows that measured cardiovascular risk and disease burden differ markedly across care settings and data-capture contexts. CVD phenotype prevalence increased with accumulated hypertension, diabetes, and dyslipidemia, and women with CVD phenotypes were older than men in primary-care and acute registry settings. These findings support sex-aware cardiovascular prevention across aging, international real-world cohorts.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1083-H1089"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688343","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":"Role of epigenetic factors during blockade of the renin-angiotensin system across aging.","authors":"Elena M V de Cavanagh, Felipe Inserra, León Ferder","doi":"10.1152/ajpheart.00417.2026","DOIUrl":"10.1152/ajpheart.00417.2026","url":null,"abstract":"<p><p>In the present article, we aimed to determine whether the beneficial effects of renin-angiotensin system (RAS) blockade on aging involve epigenetic changes and the participation of any of the cell-rejuvenating Yamanaka factors. To this end, we have reviewed published work that investigated aging and its relation to epigenetic modifications, the effects of RAS blockade on aging and epigenetics, RAS's influence on stem cell function, and RAS interactions with the Yamanaka factors KLF4, Oct4, c-Myc, and Sox2. The reviewed information indicates that it is reasonable to propose that RAS inhibition during aging will promote stem cell self-renewal by counteracting the damaging effects of tissue RAS overactivation. Also, experimental data showed that angiotensin II (ANG II) type I receptor blockade reverses the deleterious epigenetic changes promoted by ANG II overactivation. RAS blockade was shown to directly or indirectly affect the expression of the Yamanaka factors. Solid data on the interaction between RAS and the latter transcription factors is lacking. Therefore, it can only be speculated that, among other mechanisms, modification of Yamanaka factor's expression contributes to the beneficial actions of RAS blockade in aging. In conclusion, the recently described epigenetic effects of RAS inhibitors lend further support to the concept of repurposing their use as therapeutic agents to counteract the aging process.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1151-H1171"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811840","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":"Between-visit reproducibility of cerebrovascular and cardiovascular reactivity during the cold pressor test.","authors":"Joseph D Vondrasek, Jonathan W Hoch, Mu Huang, Luke N Belval, Caitlin P Jarrard, Craig G Crandall, Joseph C Watso","doi":"10.1152/ajpheart.00226.2026","DOIUrl":"10.1152/ajpheart.00226.2026","url":null,"abstract":"<p><p>The cold pressor test (CPT) is a painful test used to assess cardiovascular and cerebrovascular reactivity. Past studies examined between-visit reproducibility of cardiovascular reactivity during the CPT but not cerebrovascular reactivity. Therefore, we performed a retrospective analysis to test the hypothesis that cerebrovascular responses during the CPT would not differ and would have moderate relative agreement between visits. Fifty young adults free from overt disease, not taking pain-modifying medications, completed two trials ≥48 h apart. We measured middle cerebral artery blood velocity (MCAv) via transcranial Doppler ultrasound, beat-to-beat blood pressure (BP) via photoplethysmography, and end-tidal CO₂ ([Formula: see text]) via capnography during a 5-min baseline and 2-min CPT. We calculated reactivity as the change (Δ) from baseline to the first and second minute of the CPT. There were no between-visit differences in baseline mean BP, mean MCAv, or [Formula: see text] (<i>Ps</i> ≥ 0.24). There were no between-visit differences for Δmean MCAv (<i>Ps</i> > 0.75) or Δmean BP (<i>P</i>s > 0.07). Relative agreement between visits was moderate for Δmean MCAv [intraclass correlation coefficient (ICC): Δmin-1 = 0.68, Δmin-2 = 0.72] and moderate/good for Δmean BP (ICC: Δmin-1 = 0.65, Δmin-2 = 0.80). Our data suggest that Δmean MCAv to the CPT does not differ between visits, while the relative agreement is similar to BP reactivity. Furthermore, relative agreement was higher during <i>minute 2</i> than <i>minute 1</i> for key variables. These data extend our knowledge of the reproducibility of CPT reactivity. These findings will inform future research aimed at comparing cardiovascular and cerebrovascular reactivity as health markers between groups.<b>NEW & NOTEWORTHY</b> We present novel data on between-visit cerebrovascular and cardiovascular reactivity reproducibility during the CPT. Relative agreement was stronger for BP and mean MCAv reactivity during the second minute of the CPT, suggesting that future work should use protocols >1 min. Cerebrovascular and cardiovascular variables had similar reproducibility; changes in [Formula: see text] and perceived pain significantly predicted CVCi reactivity. Controlling [Formula: see text] could improve reproducibility; future work could consider pain perception while assessing cerebrovascular reactivity to the CPT.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1419-H1432"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944100","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":"Acute exposure to cell-free mitochondrial DNA induces pregnancy-specific aortic endothelial dysfunction and organ-selective inflammation in rats.","authors":"Nataliia Hula, Reneé de Nazaré Oliveira da Silva, Desirae Escalera, Leslie Lopez, Gabrielle Kelly, Isabelle K Gorham, Megan Rowe, Taiming Liu, Arlin B Blood, Eugenia Mata-Greenwood, Xiang-Qun Hu, Lubo Zhang, Nicole R Phillips, Styliani Goulopoulou","doi":"10.1152/ajpheart.00318.2026","DOIUrl":"10.1152/ajpheart.00318.2026","url":null,"abstract":"<p><p>Pregnancy complications such as preeclampsia are associated with circulating cell-free mitochondrial DNA (mtDNA), a damage-associated molecular pattern capable of activating Toll-like receptor 9 (TLR9). We hypothesized that acute mtDNA exposure induces maternal inflammation and endothelial dysfunction during pregnancy via TLR9 activation. Nonpregnant and pregnant rats (<i>gestational days 14</i> and <i>15</i>) were treated intravenously with saline or purified mtDNA and euthanized 4 h after treatment. mtDNA increased cytokine mRNA expression in the lungs and liver of nonpregnant and pregnant rats, with magnitude varying by pregnancy status and organ. Aortas from pregnant, but not nonpregnant, rats exhibited reduced acetylcholine (ACh)-induced relaxation following mtDNA treatment (Emax, saline: 90.1 ± 3.9% vs. mtDNA: 62.1 ± 20.7% KClmax, <i>P</i> < 0.05), whereas uterine artery function was preserved, indicating vascular bed-specific effects. Ex vivo incubation of aortic rings with mtDNA ± white blood cells did not replicate in vivo findings, implicating systemic rather than direct vascular mechanisms. Nuclear DNA did not affect ACh-induced relaxation (<i>P</i> > 0.05), confirming that the vascular effects were mtDNA-specific. Pharmacological antagonism of TLR9 with ODN2088 partially attenuated mtDNA-induced maternal endothelial dysfunction. Although overt increases in vascular reactive oxygen species (ROS) were not detected, aortas from pregnant rats had reduced <i>sod-1</i> expression (<i>P</i> < 0.05) and increased endothelial nitric oxide synthase (eNOS) protein abundance (<i>P</i> < 0.05). In conclusion, acute mtDNA exposure during pregnancy induces maternal organ inflammation and impairs endothelium-dependent vasodilation, with partial TLR9 involvement. Aortic transcriptional changes in antioxidant pathways and increased eNOS abundance were also observed, though their functional significance remains to be determined.<b>NEW & NOTEWORTHY</b> To our knowledge, this is the first study to demonstrate that acute exposure to circulating mtDNA induces pregnancy-specific maternal endothelial dysfunction and organ-selective inflammatory responses. Our findings reveal pregnancy- and vascular-bed-specific responses of the maternal vasculature to mitochondrial danger signals, with partial TLR9 involvement. Aortic transcriptional changes in antioxidant pathways and increased nitric oxide synthase abundance were identified as molecular correlates of this dysfunction.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1133-H1150"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787100","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":"Tobacco and marijuana induce adverse effects on cardiac function and platelet activity and reduce tissue preservation following myocardial infarction.","authors":"Xiaoyin Wang, Daniel D Han, Huiliang Qiu, Chaitanya Punnati, Natasha Goyal, Alyssa Parangan, Jayita Mukunda, Parmis Tabibiazar, Lam Tran, Kelly Tan, Arailym Kamzabek, Ronak Derakhshandeh, Matthew L Springer","doi":"10.1152/ajpheart.00407.2026","DOIUrl":"10.1152/ajpheart.00407.2026","url":null,"abstract":"<p><p>Smoking disrupts cardiac autonomic regulation, vascular biology, and platelet function; however, the acute and longer-term cardiovascular effects of resurging and emerging tobacco and marijuana products remain incompletely characterized. We investigated the impact of exposure to smoke and aerosol from several tobacco and marijuana products on cardiac function, platelet activity, and myocardial susceptibility to ischemia-reperfusion myocardial infarction (MI). Male and female Sprague-Dawley rats underwent single or daily 5-min pulsatile exposure sessions to emissions from tobacco cigarettes, e-cigarettes (JUUL), heated tobacco products (IQOS), marijuana cigarettes, or cannabinoid-depleted (\"placebo\") marijuana cigarettes, with an air negative control. Cardiac function was assessed immediately after single exposure by echocardiography and intraventricular hemodynamics. Platelet aggregation was measured immediately after single exposure and 1 day after repeated (2-wk) exposure. Myocardial infarct size, normalized to area at risk, was assessed following MI after repeated (4-wk) exposure. Single exposure to tobacco smoke or JUUL aerosol reduced left ventricular ejection fraction relative to preexposure. Acute marijuana smoke exposure similarly impaired left ventricular function assessed by hemodynamics. Single exposure to tobacco, marijuana, and placebo marijuana smoke increased collagen-induced platelet aggregation, with more pronounced responses in females, whereas repeated (2-wk) exposure to smoke/aerosol from tobacco cigarettes, JUUL, IQOS, and placebo marijuana increased platelet aggregation across groups. Notably, repeated (4-wk) exposure to tobacco smoke/aerosol or marijuana smoke before MI reduced myocardial tissue preservation, resulting in greater infarct size post MI. These findings indicate that individual tobacco and marijuana smoking and vaping similarly impair cardiac function, enhance platelet reactivity, and reduce myocardial tolerance to ischemia-reperfusion injury.<b>NEW & NOTEWORTHY</b> Inhalable products marketed as reduced-harm alternatives to combustible cigarettes, including e-cigarettes, heated tobacco products, and marijuana, produce rapid and sustained adverse cardiovascular effects. Even brief exposure impairs cardiac function and enhances platelet aggregation, whereas prior exposure increases myocardial susceptibility to ischemia-reperfusion injury, resulting in larger infarcts following myocardial infarction. These findings challenge the perception that noncombustible or \"reduced-harm\" products are cardiovascularly benign.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1023-H1036"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787229","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":"Local endothelin-1 receptor type A antagonism improves cutaneous microvascular function in women with a history of gestational diabetes mellitus.","authors":"Grace S Maurer, Kara M Whitaker, Diana I Jalal, Anna E Stanhewicz","doi":"10.1152/ajpheart.00541.2026","DOIUrl":"10.1152/ajpheart.00541.2026","url":null,"abstract":"<p><p>Women with a history of gestational diabetes mellitus (GDM) are at a greater risk of developing cardiovascular disease (CVD) compared with women who had an uncomplicated pregnancy. Microvascular endothelial dysfunction, mediated in part by reduced nitric oxide (NO)-dependent mechanisms, persists after GDM and contributes to vascular disease progression. Endothelin-1 (ET-1), a potent vasoconstrictor, contributes to vascular dysfunction in diabetes and may similarly contribute to vascular dysfunction after GDM. We hypothesized that local ET-1 receptor type A (ET_AR) antagonism would improve endothelium- and NO-dependent dilation in the cutaneous microvasculature of women with a history of GDM. Two intradermal microdialysis fibers were placed in the skin of the ventral forearm of 12 healthy controls (HC, 35 ± 3 yr) and 12 women with a history of GDM (34 ± 4 yr) for the local delivery of lactated Ringer's (control) or 500 nmol/L BQ-123 (ET_AR antagonist) during a standard local heating protocol (42°C; 0.1°C·s^-1). After full expression of the local heating response, 15 mmol/L <i>N</i>^G-nitro-l-arginine methyl ester (NO synthase inhibitor) was perfused. Red blood cell flux was measured by laser-Doppler flowmetry (LDF), and cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and normalized to maximum (28 mmol/L sodium nitroprusside + 43°C). Endothelium- (<i>P</i> = 0.04) and NO-dependent (<i>P</i> = 0.03) dilation were attenuated at the Ringer's site in GDM compared with HC women. In GDM women, ET_AR antagonism increased endothelium- (vs. Ringer's; <i>P</i> = 0.03) and NO-dependent (vs. Ringer's; <i>P</i> = 0.01) dilation but had no effect in HC (<i>P</i> > 0.05). These data suggest that ET-1 contributes to microvascular dysfunction following pregnancy complicated by GDM.<b>NEW & NOTEWORTHY</b> Women who experienced gestational diabetes are at a high risk of developing cardiovascular disease later in life. This risk may be mediated, in part, by endothelial dysfunction after pregnancy. We demonstrate that endothelin-1 receptor type A antagonism with BQ-123 improves microvascular endothelial responses to local heating in otherwise healthy women with a history of gestational diabetes. These findings suggest that ET-1 contributes to microvascular endothelial dysfunction after gestational diabetes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1191-H1198"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910677","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}