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

{"title":"Cardiac Energy Metabolism in Diabetes: Emerging Therapeutic Targets and Clinical Implications.","authors":"Archee Panwar, Sufyan Malik, Muhtasim Adib, Gary D Lopaschuk","doi":"10.1152/ajpheart.00615.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00615.2024","url":null,"abstract":"<p><p>Patients with diabetes are at an increased risk for developing diabetic cardiomyopathy and other cardiovascular complications. Alterations in cardiac energy metabolism in diabetic patients, including an increase in mitochondrial fatty acid oxidation and a decrease in glucose oxidation are important contributing factors to this increase in cardiovascular disease. A switch from glucose oxidation to fatty acid oxidation not only decreases cardiac efficiency due to increased oxygen consumption, but it can also increase reactive oxygen species production, increase lipotoxicity, and redirect glucose into other metabolic pathways that, combined, can lead to heart dysfunction. Currently, there is a lack of therapeutics available to treat diabetes-induced heart failure that specifically target cardiac energy metabolism. However, it is becoming apparent that part of the benefit of existing agents such as GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors may be related to their effects on cardiac energy metabolism. In addition, direct approaches aimed at inhibiting cardiac fatty acid oxidation or increasing glucose oxidation hold future promise as potential therapeutic approaches to treat diabetes-induced cardiovascular disease.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794412","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":"Transport Across the Thoracic Aortic Wall: Implications for Aneurysm Pathobiology, Diagnosis, and Treatment.","authors":"Keshav A Kailash, Shamimur R Akanda, Alexandra L Davis, Christie L Crandall, Mohamed S Zaghoul, Lori Setton, Carmen M Halabi, Mohamed A Zayed, Jessica E Wagenseil","doi":"10.1152/ajpheart.00886.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00886.2024","url":null,"abstract":"<p><p>Thoracic aortic aneurysms (TAAs) are a dilation of the aorta that may fatally dissect or rupture. The current clinical management for TAA is continuous monitoring and surgical replacement once the aortic diameter reaches a specified size or rate of growth. While operative intervention is often successful in preventing fatal outcomes, not all patients will reach surgical criteria before an aortic event, and the surgery carries significant risk with a potential requirement for reoperation. There is a need for patient-specific diagnostic tools and/or novel therapeutics to treat TAA. In this review we discuss fluid and solute transport through the aortic wall (transmural aortic transport), its potential contributions to TAA progression, and possible applications for diagnosis and treatment. We first discuss the structural organization of the aortic wall with a focus on cellular and extracellular matrix (ECM) changes associated with TAA that may alter transmural transport. We then focus on aortic transmural transport processes defined with biphasic and multiphasic theory. Biphasic theory describes fluid interactions with a porous solid (i.e., the aortic wall), while multiphasic theory describes fluid and solute(s) interactions with a porous solid. We summarize experimental and computational methods to quantify transport through the aortic wall. Finally, we discuss how transmural transport may be used to diagnose, monitor, or treat TAA. Further understanding of transmural transport may lead to new insights into TAA pathobiology and future clinical solutions.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794416","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":"Carotid artery stiffness mechanisms, heart failure events, and atrial fibrillation in MESA: the Multi-Ethnic Study of Atherosclerosis.","authors":"Ryan Pewowaruk, Claudia E Korcarz, David A Bluemke, Mohamed H Hamdan, Susan R Heckbert, Joao A C Lima, Yacob Tedla, Adam D Gepner","doi":"10.1152/ajpheart.00047.2025","DOIUrl":"10.1152/ajpheart.00047.2025","url":null,"abstract":"<p><p>Arterial stiffness can be separated into two main mechanisms: <i>1</i>) load-dependent stiffening from higher blood pressure and <i>2</i>) structural stiffening due to remodeling of the vessel wall. The relationship of stiffness mechanisms with heart failure (HF) and atrial fibrillation (AF) is unknown. MESA (multi-ethnic study of atherosclerosis) participants with baseline carotid ultrasound images were included in this study (HF <i>n</i> = 6,278; AF <i>n</i> = 5,292). Carotid pulse wave velocity (cPWV) was calculated from B-mode carotid ultrasound to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mmHg blood pressure with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Associations with incident heart failure events and atrial fibrillation diagnosis were assessed with adjusted Cox hazard models. Four hundred-seven HF events and 1,157 AF diagnoses occurred during a median 17.7 and 16.8 years of follow-up. The associations of carotid artery stiffness mechanisms with HF events were: total cPWV adjusted HR per 1 SD 1.09 [0.98-1.22], <i>P</i> = 0.11; structural cPWV adjusted HR 1.06 [0.94-1.18], <i>P</i> = 0.33; and load-dependent PWV adjusted HR 1.23 [1.05-1.44] per 1 m/s, <i>P</i> = 0.009. The associations of carotid artery stiffness mechanisms with AF diagnoses were: total cPWV adjusted HR 1.11 (1.04-1.20), <i>P</i> = 0.004; structural cPWV adjusted HR 1.10 [1.02-1.16], <i>P</i> = 0.017; load-dependent cPWV adjusted HR 1.12 [1.02-1.23], <i>P</i> = 0.020. Both structural and load-dependent cPWV were associated with the development of AF, and load-dependent cPWV was associated with HF events. These findings indicate that load-dependent cPWV may be a potential treatment target to reduce the incidence of both HF and AF.<b>NEW & NOTEWORTHY</b> We evaluated associations between novel components of arterial stiffness: <i>1</i>) load-dependent stiffening from higher blood pressure and <i>2</i>) structural stiffening due to remodeling of the vessel wall and their associations with incident heart failure (<i>n</i> = 6,278) and atrial fibrillation (<i>n</i> = 5,292) over ∼17 years of follow-up. We found that both baseline structural and load-dependent stiffness were associated with the development of atrial fibrillation and load-dependent stiffness was associated with heart failure events.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1019-H1025"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668895","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":"Exploring the mechanisms of sex-specific proarrhythmia in long QT syndrome through computational modeling.","authors":"Isabella Doherty, Roshni Shetty, Haibo Ni, Stefano Morotti, Eleonora Grandi","doi":"10.1152/ajpheart.00792.2024","DOIUrl":"10.1152/ajpheart.00792.2024","url":null,"abstract":"<p><p>Females exhibit longer QT intervals and a higher risk of long QT syndrome (LQTS) associated arrhythmogenesis compared with males. Although several studies suggest these sex disparities result from the effect of sex hormones on cardiac ion channels, the underlying mechanisms remain incompletely understood. This research investigates the arrhythmogenic effects, sex-specific risk, and mechanisms associated with LQTS linked to either to loss-of-function of the rapidly activating delayed rectifier K⁺ current (<i>I</i>_Kr), or gain-of-function of the L-type Ca²⁺ current (<i>I</i>_CaL). We primarily used the Tomek-Rodriguez (ToR-ORd) model of human ventricular cardiomyocytes and incorporated sex-specific parameterizations based on previous studies. The O'Hara-Rudy and Grandi-Bers models were used to demonstrate model-independence of the findings. We used a populations-of-models approach to assess early afterdepolarization (EAD) susceptibility in control and LQTS male and female groups. All female models had consistently longer action potentials and were more prone to EADs than male models. In the ToR-ORd model, <i>I</i>_Kr loss-of-function led to EADs in 65.8% of females versus 22.8% of males. <i>I</i>_CaL gain-of-function led to EADs in 66.2% of females but only 3.6% of males. Using logistic regression analysis, we identified key ionic predictors of EAD susceptibility, with maximal conductance of the L-type Ca²⁺ current (<i>G</i>_CaL) and maximal transport rate of the Na⁺/Ca²⁺ exchanger (<i>G</i>_NCX) consistently emerging as positively and maximal conductance of the rapidly activating delayed rectifier K⁺ current (<i>G</i>_Kr) as negatively associated to EADs across both sexes and LQTS types. Notably, higher <i>G</i>_NCX but lower <i>G</i>_Kr in female versus male cardiomyocytes could explain heightened female EAD risk. Our studies explore the ionic traits that favor (or confer resilience against) EADs with potential implications for personalized treatments. <b>NEW & NOTEWORTHY</b> We explored sex disparities in long QT syndrome (LQTS) using sex-specific human ventricular cardiomyocyte models. We showed that females exhibit greater susceptibility to early afterdepolarizations (EADs) than males, and identified key ionic predictors of EAD risk, including increases in the voltage-gated L-type Ca²⁺ current and electrogenic Na⁺/Ca²⁺ exchanger, and downregulation of the rapidly activating delayed rectifier K⁺ current. These findings offer new insights into sex-specific mechanisms underlying arrhythmogenesis in LQTS, with potential implications for personalized treatments.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H963-H972"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623108","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":"Oxidative stress and pediatric diabetic cardiovascular complications: emerging research and clinical applications.","authors":"Saman Saedi, Yi Tan, Sara E Watson, Joshua D Sparks, Kupper A Wintergerst, Lu Cai","doi":"10.1152/ajpheart.00673.2024","DOIUrl":"10.1152/ajpheart.00673.2024","url":null,"abstract":"<p><p>The prevalence and incidence of diabetes in pediatrics have dramatically increased over the last three decades. Comparatively, pediatric diabetes has faster pancreatic β-cells decline and early progression to complications compared with adult diabetes. Therefore, diabetic complications are a major concern in children and adolescents with diabetes. Diabetes has detrimental effects on the macro- and microvascular systems, resulting in cardiovascular diseases, leading causes of morbidity and mortality in youth with diabetes. Oxidative stress plays a critical role in developing cardiovascular complications in the context of pediatric diabetes. In pediatric patients with diabetes, several factors can contribute to the development of excess reactive oxygen species and oxidative stress, including nutritional deficiencies, puberty, environmental exposures, and metabolic disorders such as obesity and high blood pressure. The present study aims to raise awareness of diabetic cardiovascular complications in children and adolescents with diabetes and the role of oxidative stress and their molecular mechanisms in the pathogenesis of cardiovascular complications. In addition, some novel therapeutic strategies for the treatment and prevention of diabetic cardiovascular complications in the pediatric populations are highlighted. In summary, children and adolescents with diabetes no matter type 1 diabetes (T1D) or type 1 diabetes (T2D), have many features similar to those in adults with same kinds of diabetes, but also have many their own features distinct from adults. By developing targeted therapies and preventive measures, healthcare providers can better address the rising incidence of diabetes-related complications in children and adolescents.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H945-H962"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522456","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":"Warm-ischemia and cold storage induced modulation of ferroptosis observed in human hearts donated after circulatory death and brain death.","authors":"Shiyi Li, Katherine V Nordick, Abdussalam E Elsenousi, Rishav Bhattacharya, Randall P Kirby, Adel M Hassan, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal","doi":"10.1152/ajpheart.00806.2024","DOIUrl":"10.1152/ajpheart.00806.2024","url":null,"abstract":"<p><p>We investigated ferroptosis, a type of programmed cell death mechanism, in human hearts donated after brain death (DBD) and those donated after circulatory death (DCD), focusing on warm ischemia time (WIT) and cold storage. A total of 24 hearts were procured, with six from the DBD group and 18 from the DCD group. The DCD group was divided into three subgroups, each containing six hearts, based on different WITs of 20, 40, and 60 min. All procured hearts were placed in cold storage for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h. We measured ferroptosis regulators [glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long chain family member 4 (ACSL4), and transferrin receptor], iron content (Fe²⁺ and Fe³⁺), and lipid peroxidation (malondialdehyde, MDA) in the cardiac tissue. Modulation of ferroptosis was observed in both DBD and DCD hearts. Warm ischemia injury increased myocardial vulnerability to ferroptotic cell death. For DBD hearts, up to 6 h of cold storage increases cardiac levels of MDA, iron content, and ACSL4, thereby increasing vulnerability to ferroptotic cell death. In contrast, for DCD hearts with a WIT of 40 min or more, warm ischemia injury was identified as the primary factor contributing to increased myocardial susceptibility to ferroptotic cell death. Ferroptosis may serve as a promising target to optimize cold preservation for DBD hearts. For DCD hearts, strategies to inhibit ferroptosis should focus on the early warm ischemia phase to assess donor heart quality and suitability for transplantation.<b>NEW & NOTEWORTHY</b> The first human heart research explored the effects of ischemia on the myocardial ferroptotic cell death mechanism. Prolonged cold storage increases the susceptibility of DBD hearts to ferroptotic cell death. In contrast, warm ischemic injury appears to be the main factor leading to the vulnerability of DCD heart ferroptosis. Targeting ferroptosis could be beneficial in optimizing cold preservation for DBD hearts. However, for DCD hearts, interventions should focus on the early phase of warm ischemia.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H923-H936"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584163","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":"Elevated frame rates during exercise echocardiography improve speckle-tracking success rate and augment deformation values.","authors":"Fabian Spahiu, Michelle Ottlik, Lars C Helbig, Eric J Stöhr","doi":"10.1152/ajpheart.00817.2024","DOIUrl":"10.1152/ajpheart.00817.2024","url":null,"abstract":"<p><p>Although two-dimensional (2-D) speckle-tracking echocardiography (STE) is important for the clinical quantification of myocardial function, it remains unknown whether increased frame rates during exercise STE augment tracking success and absolute deformation values. Overall, 19 participants (15 males and 4 females; aged 26.7 ± 4.8) underwent stepwise exercise testing on a recumbent bicycle. Exercise started at 50 W, increasing by 30 W every 3 min until a target heart rate (HR) of 130-140 beats/min was reached. During the last 90 s of each exercise stage, echocardiographic sequences for offline quantification of longitudinal strain (LS), peak twist, untwisting velocity, basal rotation, and apical rotation were acquired with high [high frames per second (HFPS)], medium [medium frames per second (MFPS)], and low-frames per second (LFPS)]. Differences in tracking success were determined by using Chi-square test, and the impact of different frame rates on absolute deformation values was compared by using mixed-model analysis. Utilization of HFPS significantly improved tracking success for parasternal short-axis images. LS acquired at HFPS was the highest at baseline and across all the exercise stages. Similar trends were observed for twist, peak untwisting velocity, and apical rotation, whereas basal rotation showed no differences. Mixed-model analysis revealed a significant impact of frame rate setting on LS (<i>P</i> < 0.05) and untwisting velocity (<i>P</i> < 0.05). In contrast to recommendations by leading organizations advocating for frame rates between 40 and 80 frames per second (fps) during resting conditions, with a proportional increase as heart rate rises, our findings suggest that consistently maintaining the frame rate at the highest feasible level is preferable for achieving optimal-tracking success and accuracy in STE.<b>NEW & NOTEWORTHY</b> This study demonstrates the benefits of high frame per second (HFPS) rate settings in speckle-tracking echocardiography, achieving superior-tracking success and higher deformation values, including longitudinal strain and untwisting velocity, compared with lower frame rates. These advantages, particularly evident at elevated heart rates, highlight the importance of high temporal resolution for accurate cardiac imaging under stress conditions. The findings support prioritizing HFPS in clinical and research settings to improve tracking reliability and data accuracy.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H752-H760"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063093","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":"Endothelial dysfunction promotes age-related reorganization of collagen fibers and alters aortic biomechanics in mice.","authors":"Liya Du, Jeffrey Rodgers, Nazli Gharraee, Olivia Gary, Tarek Shazly, John F Eberth, Susan M Lessner","doi":"10.1152/ajpheart.00056.2023","DOIUrl":"10.1152/ajpheart.00056.2023","url":null,"abstract":"<p><p>Endothelial dysfunction, defined as a reduction in the bioavailability of nitric oxide (NO), is a risk factor for the occurrence and progression of various vascular diseases. This study investigates the effect of endothelial dysfunction on age-related changes in aortic extracellular matrix (ECM) microstructure and the relationship between microstructural adaptation and the mechanical response. Here, we used groups of NOS3 knockout (KO), NOS3 heterozygotes (Het), and wild-type (WT) B6 mice (controls) to study changes in hemodynamic parameters, collagen fiber organization, and both active and passive aortic mechanics using biaxial pressure myography over a time course from 1.5 to 12 mo. Our results show that homeostatic levels of passive circumferential stress and stretch were preserved in KO mice by remodeling adventitial collagen fibers toward a more predominantly circumferential direction with age, rather than by increased fibrosis, in response to hypertension induced by endothelial dysfunction. However, passive aortic stiffness in KO mice was significantly increased owing to geometrical changes, including significant increases in wall thickness and decreases in inner diameter, and by ECM microstructural reorganization, during this maladaptive vascular remodeling. Furthermore, long-term NO deficiency significantly increased smooth muscle cell (SMC) contractility initially, but this effect was attenuated with age. These findings improve our understanding of microstructural and mechanical changes during the maladaptive vascular remodeling process, demonstrating a role for adventitial collagen fiber reorientation in the response to hypertension.<b>NEW & NOTEWORTHY</b> Endothelial dysfunction facilitates the reorganization of collagen fibers toward a more predominantly circumferential orientation with age, consequently promoting homeostatic normalization of passive circumferential stress and stretch in the vessel subjected to hypertension.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H900-H914"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584401","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":"Aortic aneurysm and dissection: complement and precision medicine in aortic disease.","authors":"Leonie Dreher, Malte B Kuehl, Ulrich O Wenzel, Dominik Kylies","doi":"10.1152/ajpheart.00853.2024","DOIUrl":"10.1152/ajpheart.00853.2024","url":null,"abstract":"<p><p>Aortic disease encompasses life-threatening conditions such as aortic aneurysm and dissection, which are associated with high prevalence, morbidity, and mortality. The complement system, a key component of innate immunity, not only defends against pathogens but also maintains tissue homeostasis. Recent discoveries have expanded its role beyond immunity, linking complement dysregulation to numerous diseases and positioning it as a target for pharmacotherapy. Complement-based treatments for precision medicine are emerging, with several pharmaceuticals either already approved or under investigation. In aortic disease, complement activation and dysregulation have unveiled novel mechanisms and clinical implications. Human and experimental studies suggest that all three complement pathways contribute to disease pathophysiology. The complement system induces direct cellular damage via the membrane attack complex, as well as matrix-metalloproteinase (MMP)-associated tissue damage by promoting MMP-2 and MMP-9 expression. The anaphylatoxins C3a and C5a exacerbate disease by recruiting immune cells and triggering proinflammatory responses. Examples include neutrophil extracellular trap formation and cytokine release by polymorphonuclear neutrophils. These findings highlight the complement system as a promising novel diagnostic and therapeutic target in aortic disease with potential for individualized treatment. However, gaps remain, emphasizing the need for standardized multisite preclinical studies to improve reproducibility and translation. Biomarker studies must also be validated across diverse patient cohorts for clinical applicability. This review examines current knowledge regarding complement in aortic disease, aiming to evaluate its potential for innovative diagnostic and personalized treatment strategies.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H814-H829"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527825","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":"Prognostic circulatory signature metabolites of stable versus unstable angina: an application of NMR spectroscopy.","authors":"Ashish Gupta, Shiridhar Kashyap, Deepak Kumar, Khushbhu Meena, Anupam Kumar, Ankit Kumar Sahu, Sudeep Kumar, Aditya Kapoor","doi":"10.1152/ajpheart.00707.2024","DOIUrl":"10.1152/ajpheart.00707.2024","url":null,"abstract":"<p><p>In spite of the ongoing efforts to probe the metabolic signatures of stable (SA) from unstable (UA) angina, it is concerning that to date there are no clinically validated circulatory biochemical signatures against the intrinsic anatomical changes that are screened by invasive coronary angiography. Hence, the aim of this study is to generate precise biochemical fingerprints using filtered serum-based metabolomics and high-throughput nuclear magnetic resonance (NMR) spectroscopy to accurately distinguish the metabolic signatures of patients suffering with SA or UA angina. The study includes 118 filtered serum samples from patients suffering from UA (<i>n</i> = 50) and SA (<i>n</i> = 68). High-resolution NMR spectroscopy was used to assess the metabolic remodeling in these cohorts. Subsequently, principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and artificial neural network (ANN) analysis were adapted to engender a precise prediction model. Analysis of the receiver operating characteristic (ROC) curve was conducted to determine the clinical usefulness of metabolic markers. The outcome revealed that the metabolic profile for the underlying disease is characterized by altered metabolite levels in UA relative to SA. Creatinine, 3-OH butyrate, and aspartate level could differentiate 100% of UA from SA with 100% sensitivity and specificity. To monitor and determine UA from patients with SA, ¹H NMR-based filtered serum metabolic profiling seems to be a promising, less invasive, and faster investigative approach.<b>NEW & NOTEWORTHY</b> There are no metabolic signatures present to identify unstable from stable angina. Coronary angiography identifies anatomical changes after the event of unstable angina, but NMR-based metabolomics identifies unstable from stable angina within 4 h. Creatinine, 3-OH butyrate, and aspartate were able to segregate unstable from stable angina.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H761-H773"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490384","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}