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

{"title":"Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.","authors":"Guido E Pieles, Dan-Mihai Dorobantu, Jessica E Caterini, Barbara Cifra, Janette Reyes, Sara Roldan Ramos, Eilis Hannon, Craig A Williams, Tilman Humpl, Luc Mertens, Greg D Wells, Mark K Friedberg","doi":"10.1152/ajpheart.00096.2024","DOIUrl":"10.1152/ajpheart.00096.2024","url":null,"abstract":"<p><p>Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age of 13.4 ± 2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ± 25 mmHg at rest to 130 ± 40 mmHg at peak exercise (<i>P</i> < 0.001), whereas RV fractional area change (RV-FAC) and RV-free wall longitudinal strain (RVFW-S_l) worsened (35.2 vs. 27%, <i>P</i> = 0.09 and -16.6 vs. -14.6%, <i>P</i> = 0.1, respectively). At low- and moderate-intensity exercise, RVsp was positively associated with stroke volume and O₂ pulse (<i>P</i> < 0.1). At high-intensity exercise, RV-FAC, RVFW-S_l, and left ventricular longitudinal strain were positively associated with oxygen uptake and O₂ pulse (<i>P</i> < 0.1), whereas stroke volume decreased toward peak (<i>P</i> = 0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV to pulmonary artery (RV-PA) uncoupling, worsening of interventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.<b>NEW & NOTEWORTHY</b> In children with pulmonary arterial hypertension, there is a marked increase in pulmonary artery pressure during physical activity, but this is not the underlying mechanism that limits exercise. Instead, right ventricle-to-pulmonary artery uncoupling occurs at the transition from moderate to high-intensity exercise and correlates with lower peak oxygen uptake. This highlights the more complex underlying pathological responses and the need for multiparametric assessment of cardiac function reserve in these patients when feasible.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756648","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":"Effects of excess sodium consumption on arterial function in C57BL/6 mice.","authors":"Mostafa Sabouri, Xiangyu Zheng, Bryan J Irwin, Daniel R Machin","doi":"10.1152/ajpheart.00242.2024","DOIUrl":"10.1152/ajpheart.00242.2024","url":null,"abstract":"<p><p>Excess sodium consumption contributes to arterial dysfunction in humans. The C57BL/6 strain of mice has been used to identify mechanisms by which arterial dysfunction occurs after excess sodium consumption. However, there are concerns that C57BL/6 mice have strain-specific resistance to high-sodium (HS) diet-induced hypertension. To address this concern, we performed a meta-analysis to determine if excess sodium consumption in C57BL/6 mice induces arterial dysfunction. Databases were searched for HS versus standard diet studies that measured arterial function [i.e., systolic blood pressure (BP), endothelium-dependent dilation (EDD), and central arterial stiffness] in C57BL/6 mice. A total of 39 studies were included, demonstrating that the HS condition resulted in higher systolic BP than control mice with a mean difference of 9.8 mmHg (95% confidence interval [CI] = [5.6, 14], <i>P</i> < 0.001). Subgroup analysis indicated that the systolic BP was higher in HS compared with the control condition when measured during night compared with daytime with telemetry (<i>P</i> < 0.001). We also identified that the difference in systolic BP between HS and control was ∼2.5-fold higher when administered through drinking water than through food (<i>P</i> < 0.001). A total of 12 studies were included, demonstrating that the HS condition resulted in lower EDD than control with a weighted mean difference of -12.0% (95% CI = [-20.0, -4.1], <i>P</i> = 0.003). It should be noted that there was considerable variability across studies with more than half of the studies showing no effect of the HS condition on systolic BP or EDD. In summary, excess sodium consumption elevates systolic BP and impairs EDD in C57BL/6 mice.<b>NEW & NOTEWORTHY</b> C57BL/6 mice are perceived as resistant to high-sodium diet-induced arterial dysfunction. This meta-analysis demonstrates that excess sodium consumption elevates blood pressure and impairs endothelium-dependent dilation in C57BL/6 mice. Nighttime measurements show more pronounced blood pressure elevation. In addition, sodium administration via drinking water, compared with food, induces a greater blood pressure elevation. These findings may be influenced by outlier studies, as the majority of studies showed no adverse effect of excess sodium consumption on arterial function.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987294","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":"Global genomic profile of hippocampal endothelial cells by single-nuclei RNA sequencing in female diabetic mice is associated with cognitive dysfunction.","authors":"Dragan Milenkovic, Saivageethi Nuthikattu, Jennifer E Norman, Amparo C Villablanca","doi":"10.1152/ajpheart.00251.2024","DOIUrl":"10.1152/ajpheart.00251.2024","url":null,"abstract":"<p><p>Type II diabetes mellitus (T2D) is a chronic metabolic disease and a risk factor for cardiovascular disease and cerebrovascular dysfunction including vascular dementia. Sex differences in the prevalence of T2D, dementia, and global genomic changes in the brain have been observed; however, most studies have been performed in males. Therefore, our aim was to evaluate the consequence of T2D on cognitive function and decipher the underlying molecular transcriptomic mechanisms of endothelial cells in an important brain memory center, the hippocampus, using a female murine diabetes model. We assessed cognitive function, metabolic parameters, and then performed hippocampal single-nuclei RNA sequencing (snRNA seq) in adult female <i>db/db</i> and control wild-type (WT) mice. <i>db/db</i> mice exhibited characteristic T2D metabolism with hyperglycemia, hyperinsulinemia, and hyperlipidemia when compared with WT mice. Female <i>db/db</i> mice presented cognitive decline compared with wild-type mice, as determined by open field and Morris water maze tests. snRNAseq showed that T2D induced significant changes in the global transcriptomic profile of hippocampal endothelial cells by modulating the expression of not only protein-coding genes but also long noncoding RNAs. These genes regulate cell-cell junctions, cell chemotaxis, actin cytoskeleton organization, and cell adhesion, suggesting that diabetes increases endothelial cell permeability. Observed genomic changes also correlated with the genetics of persons with clinical Alzheimer's disease and vascular dementia. In conclusion, T2D, by transcriptional and posttranscriptional regulation, regulates endothelial cell dysfunction predictive of increased vascular permeability, and negatively impacts cognitive function. Our work has implications for sex-specific molecular therapeutic targets for dementia in females.<b>NEW & NOTEWORTHY</b> Female <i>db/db</i> mice presented cognitive decline as determined by open field and Morris water maze tests. snRNAseq showed that T2D induced changes in the global transcriptomic profile of hippocampal endothelial cells by modulating the expression of not only protein-coding genes but also long noncoding RNAs. These genes regulate cell-cell junctions, cell chemotaxis, or cell adhesion, suggesting increased endothelial permeability. Genomic changes correlated with the genetics of persons with clinical Alzheimer's disease and vascular dementia.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987296","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":"Constipation is associated with an increased risk of major adverse cardiac events in a UK population.","authors":"Tenghao Zheng, Leticia Camargo Tavares, Mauro D'Amato, Francine Z Marques","doi":"10.1152/ajpheart.00519.2024","DOIUrl":"10.1152/ajpheart.00519.2024","url":null,"abstract":"<p><p>Traditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACEs). Understanding what other risk factors contribute to MACE is essential for prevention. Constipation shares common risk factors with hypertension and is associated with an increased risk of several cardiovascular diseases. We hypothesized that constipation is an underappreciated risk factor for MACE. We used the population healthcare and genomic data in the UK Biobank (<i>n</i> = 408,354) to study the contribution of constipation (ICD10 K59.0) to the risk of MACE, defined by any episode of acute coronary syndrome (ACS), ischemic stroke, and heart failure (HF). Analyses were controlled for traditional cardiovascular risk factors. We also assessed genetic correlations (<i>r</i>_g) between constipation and MACE. Constipation cases (<i>n =</i> 23,814) exhibited a significantly higher risk of MACE compared with those with normal bowel habits [odds ratio (OR) = 2.15, <i>P</i> < 1.00 × 10^-300]. Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR = 2.72, <i>P</i> < 1.00 × 10^-300), ischemic stroke (OR = 2.36, <i>P</i> = 2.02 × 10^-230), and ACS (OR = 1.62, <i>P</i> = 5.82 × 10^-113). In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE (OR = 1.68, <i>P</i> = 1.05 × 10^-136) and a 34% increased risk of MACE occurrence (<i>P</i> = 2.3 × 10^-50) after adjustment for medications that affect gut motility and other traditional cardiovascular risk factors. Finally, we detected positive genetic correlations between constipation and MACE subgroups ACS (<i>r</i>_g = 0.27, <i>P</i> = 2.12 × 10^-6), ischemic stroke (<i>r</i>_g = 0.23, <i>P</i> = 0.011), and HF (<i>r</i>_g = 0.21, <i>P</i> = 0.0062). We identified constipation as a potential risk factor independently associated with higher MACE prevalence. These findings warrant further studies on their causal relationship and identification of pathophysiological mechanisms.<b>NEW & NOTEWORTHY</b> Analyzing 408,354 participants of the UK Biobank, we show that constipation cases exhibited a significantly higher risk of major adverse cardiac events (MACEs) than those with regular bowel habits. In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE and a 34% increased risk of subsequent MACE occurrence. Finally, we detected positive genetic correlations between constipation and MACE. This association holds potential for therapeutic exploitation and prevention based on individuals' risk assessment.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987293","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":"Integrating molecular and cellular components of endothelial shear stress mechanotransduction.","authors":"Gavin Power, Larissa Ferreira-Santos, Luis A Martinez-Lemus, Jaume Padilla","doi":"10.1152/ajpheart.00431.2024","DOIUrl":"10.1152/ajpheart.00431.2024","url":null,"abstract":"<p><p>The lining of blood vessels is constantly exposed to mechanical forces exerted by blood flow against the endothelium. Endothelial cells detect these tangential forces (i.e., shear stress), initiating a host of intracellular signaling cascades that regulate vascular physiology. Thus, vascular health is tethered to the endothelial cells' capacity to transduce shear stress. Indeed, the mechanotransduction of shear stress underlies a variety of cardiovascular benefits, including some of those associated with increased physical activity. However, endothelial mechanotransduction is impaired in aging and disease states such as obesity and type 2 diabetes, precipitating the development of vascular disease. Understanding endothelial mechanotransduction of shear stress, and the molecular and cellular mechanisms by which this process becomes defective, is critical for the identification and development of novel therapeutic targets against cardiovascular disease. In this review, we detail the primary mechanosensitive structures that have been implicated in detecting shear stress, including junctional proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1), the extracellular glycocalyx and its components, and ion channels such as piezo1. We delineate which molecules are truly mechanosensitive and which may simply be indispensable for the downstream transmission of force. Furthermore, we discuss how these mechanosensors interact with other cellular structures, such as the cytoskeleton and membrane lipid rafts, which are implicated in translating shear forces to biochemical signals. Based on findings to date, we also seek to integrate these cellular and molecular mechanisms with a view of deciphering endothelial mechanotransduction of shear stress, a tenet of vascular physiology.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034973","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":"One day of environment-induced heat stress damages the murine myocardium.","authors":"Melissa Roths, Tori E Rudolph, Swathy Krishna, Alyona Michael, Joshua T Selsby","doi":"10.1152/ajpheart.00180.2024","DOIUrl":"10.1152/ajpheart.00180.2024","url":null,"abstract":"<p><p>The physiological consequences of environment-induced heat stress (EIHS), caused by prolonged exposure to excess heat and humidity, are largely unknown. The purpose of this investigation was to determine the extent to which EIHS alters cardiac health. We hypothesized that 24 h of EIHS would cause cardiac injury and cellular dysfunction in a murine EIHS model. To test this hypothesis, 7-wk-old female mice were housed under thermoneutral (TN) conditions (<i>n</i> = 12; 31.2 ± 1.01°C, 35 ± 0.7% humidity) or EIHS conditions (<i>n</i> = 14; 37.6 ± 0.01°C, 42.0 ± 0.06% humidity) for 24 h. Environment-induced heat stress increased rectal temperature by 2.1°C (<i>P</i> < 0.01) and increased subcutaneous temperature by 1.8°C (<i>P</i> < 0.01). Body weight was decreased by 10% (<i>P</i> = 0.03), heart weight/body weight was increased by 26% (<i>P</i> < 0.01), and tissue water content was increased by 11% (<i>P</i> < 0.05) in EIHS compared with TN. In comparison with TN, EIHS increased protein abundance of heat shock protein (HSP) 27 by 84% (<i>P</i> = 0.01); however, HSPs 90, 60, 70, and phosphorylated HSP 27 were similar between groups. Histological inspection of the heart revealed that EIHS animals had increased myocyte vacuolation in the left ventricle (<i>P</i> = 0.01), right ventricle (<i>P</i> < 0.01), and septum (<i>P</i> = 0.01) compared with TN animals. Biochemical indices are suggestive of mitochondrial remodeling, increased autophagic flux, and robust activation of endoplasmic reticulum stress in hearts from EIHS mice compared with TN mice. These data demonstrate that 1 day of EIHS is sufficient to induce myocardial injury and biochemical dysregulation.<b>NEW & NOTEWORTHY</b> The consequences of prolonged environment-induced heat stress (EIHS) on heart health are largely unknown. We discovered that a 24-h exposure to environmental conditions sufficient to cause EIHS resulted in cardiac edema and histopathologic changes in the right and left ventricles. Furthermore, among other biochemical changes, EIHS increased autophagic flux and caused endoplasmic reticulum stress. These data raise the possibility that thermic injury, even when insufficient to cause heat stroke, can damage the myocardium.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103579","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":"Maternal AMPK pathway activation with uterine artery blood flow and fetal growth maintenance during hypoxia.","authors":"Lorna G Moore, Ramón A Lorca, Diane L Gumina, Stephanie R Wesolowski, Julie A Reisz, Darleen Cioffi-Ragan, Julie A Houck, Sarah Banerji, Anna G Euser, Angelo D'Alessandro, John C Hobbins, Colleen G Julian","doi":"10.1152/ajpheart.00193.2024","DOIUrl":"10.1152/ajpheart.00193.2024","url":null,"abstract":"<p><p>High-altitude (HA) hypoxia lowers uterine artery (UtA) blood flow during pregnancy and birth weight. Adenosine monophosphate kinase (AMPK) activation has selective, uteroplacental vasodilator effects that lessen hypoxia-associated birth weight reductions. In this study, we determined the relationship between AMPK-pathway gene expression and metabolites in the maternal circulation during HA pregnancy as well as with the maintenance of UtA blood flow and birth weight at HA. Residents at HA (2,793 m) versus low altitude (LA; 1,640 m) had smaller UtA diameters at <i>weeks 20</i> and <i>34</i>, lower UtA blood flow at <i>week 20</i>, and lower birth weight babies. At <i>week 34</i>, women residing at HA versus women residing at LA had decreased expression of upstream and downstream AMPK-pathway genes. Expression of the α₁-AMPK catalytic subunit, <i>PRKAA1</i>, correlated positively with UtA diameter and blood flow at <i>weeks 20</i> (HA) and 34 (LA). Downstream AMPK-pathway gene expression positively correlated with <i>week 20</i> fetal biometry at both altitudes and with UtA diameter and birth weight at LA. Reduced gene expression of AMPK activators and downstream targets in women residing at HA versus women residing at LA, together with positive correlations between <i>PRKAA1</i> gene expression, UtA diameter, and blood flow suggest that greater sensitivity to AMPK activation at midgestation at HA may help offset later depressant effects of hypoxia on fetal growth.<b>NEW & NOTEWORTHY</b> Fetal growth restriction (FGR) is increased and uterine artery (UtA) blood flow is lower at high altitudes (HA) but not all HA pregnancies have FGR. Here we show that greater UtA diameter and blood flow at <i>week 20</i> are positively correlated with higher expression of the gene encoding the α₁-catalytic subunit of AMP protein kinase, <i>PRKAA1</i>, suggesting that increased AMPK activation may help to prevent the detrimental effects of chronic hypoxia on fetal growth.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726752","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 microvascular insulin-dependent dilation in women with a history of gestational diabetes.","authors":"Kelsey S Schwartz, Paola V Hernandez, Grace S Maurer, Elizabeth M Wetzel, Mingyao Sun, Diana I Jalal, Anna E Stanhewicz","doi":"10.1152/ajpheart.00223.2024","DOIUrl":"10.1152/ajpheart.00223.2024","url":null,"abstract":"<p><p>Women with a history of gestational diabetes mellitus (GDM) have a significantly greater lifetime risk of developing cardiovascular disease and type 2 diabetes compared with women who had an uncomplicated pregnancy (HC). Microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation secondary to increases in oxidative stress, persists after pregnancy complicated by GDM. We examined whether this microvascular dysfunction reduces insulin-mediated vascular responses in women with a history of GDM. We assessed in vivo microvascular endothelium-dependent vasodilator function by measuring cutaneous vascular conductance responses to graded infusions of acetylcholine (10^-10-10^-1 M) and insulin (10^-8-10^-4 M) in control sites and sites treated with 15 mM l-NAME [<i>N</i>^G-nitro-l-arginine methyl ester; NO-synthase (NOS) inhibitor] or 5 mM l-ascorbate. We also measured protein expression of total endothelial NOS (eNOS), insulin-mediated eNOS phosphorylation, and endothelial nitrotyrosine in isolated endothelial cells from GDM and HC. Women with a history of GDM had reduced acetylcholine (<i>P</i> < 0.001)- and insulin (<i>P</i> < 0.001)-mediated dilation, and the NO-dependent responses to both acetylcholine (<i>P</i> = 0.006) and insulin (<i>P</i> = 0.006) were reduced in GDM compared with HC. Insulin stimulation increased phosphorylated eNOS content in HC (<i>P</i> = 0.009) but had no effect in GDM (<i>P</i> = 0.306). Ascorbate treatment increased acetylcholine (<i>P</i> < 0.001)- and insulin (<i>P</i> < 0.001)-mediated dilation in GDM, and endothelial cell nitrotyrosine expression was higher in GDM compared with HC (<i>P</i> = 0.014). Women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and this attenuation is mediated, in part, by reduced NO-dependent mechanisms. Our findings further implicate increased endothelial oxidative stress in this microvascular insulin resistance.<b>NEW & NOTEWORTHY</b> Women who have gestational diabetes during pregnancy are at a greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. The mechanisms mediating this increased risk are unclear. Herein, we demonstrate that insulin-dependent microvascular responses are reduced in women who had gestational diabetes, despite the remission of glucose intolerance. This reduced microvascular sensitivity to insulin may contribute to increased cardiovascular disease and type 2 diabetes risk in these women.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756650","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":"Lower estimates of myocardial perfusion are associated with greater aortic perivascular adipose tissue density in humans independent of aortic stiffness.","authors":"Nicholas A Carlini, Matthew P Harber, Bradley S Fleenor","doi":"10.1152/ajpheart.00436.2024","DOIUrl":"10.1152/ajpheart.00436.2024","url":null,"abstract":"<p><p>Aortic perivascular adipose tissue (aPVAT) density is associated with age-related aortic stiffness in humans and therefore, may contribute to cardiovascular dysfunction. A lower subendocardial viability ratio (SEVR), an estimate of myocardial perfusion, indicates greater cardiovascular disease (CVD) risk and is associated with aortic stiffness in clinical populations. However, the influence of aortic stiffness on the relation between aPVAT density and SEVR/cardiovascular (CV) hemodynamics in apparently healthy adults is unknown. We hypothesize that greater aPVAT density will be associated with lower SEVR and higher CV hemodynamics independent of aortic stiffness. Fourteen (6 males/8 females; mean age, 55.4 ± 5.6 yr; body mass index, 25.5 ± 0.6 kg/m²) adults completed resting measures of myocardial perfusion (SEVR), CV hemodynamics (pulse wave analysis), aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)], and a computed tomography scan to acquire aPVAT and visceral adipose tissue (VAT) density. Greater aPVAT density (i.e., higher density) was associated with lower SEVR (<i>r</i> = -0.78, <i>P</i> < 0.001) and a higher systolic pressure time integral (<i>r</i> = 0.49, <i>P</i> = 0.03), forward pulse height (<i>r</i> = 0.49, <i>P</i> = 0.03), reflected pulse height (<i>r</i> = 0.55, <i>P</i> = 0.02), ejection duration (<i>r</i> = 0.56, <i>P</i> = 0.02), and augmentation pressure (<i>r</i> = 0.69, <i>P</i> = 0.003), but not with the diastolic pressure time integral (<i>r</i> = -0.22, <i>P</i> = 0.22). VAT density was not associated with SEVR or any CV hemodynamic endpoints (all, <i>P</i> > 0.05). Furthermore, the relation between aPVAT density and SEVR remained after adjusting for aortic stiffness (<i>r</i> = -0.66, <i>P</i> = 0.01) but not age (<i>r</i> = -0.24, <i>P</i> > 0.05). These data provide initial evidence for aPVAT as a novel yet understudied local fat depot contributing to lower myocardial perfusion in apparently healthy adults with aging.<b>NEW & NOTEWORTHY</b> Aortic perivascular adipose tissue (aPVAT) density is associated with aging and aortic stiffness in humans and, therefore, may contribute to lower myocardial perfusion. We demonstrate that greater aPVAT, but not visceral adipose tissue density is associated with lower myocardial perfusion and augmentation pressure independent of aortic stiffness, but not independent of age. These data provide novel evidence for aPVAT as a potential therapeutic target to improve myocardial perfusion and cardiovascular function in humans with aging.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987297","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":"Reactive oxygen species in cardiac electrophysiology: loss of Scn1b increases susceptibility to oxidative stress and drives a proarrhythmic phenotype.","authors":"Janet R Manning, Iain Scott","doi":"10.1152/ajpheart.00568.2024","DOIUrl":"10.1152/ajpheart.00568.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103581","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}