Cardiovascular Research最新文献

{"title":"Stretch regulation of β2-Adrenoceptor signalling in cardiomyocytes requires caveolae.","authors":"Jiarong Fu, Catherine Mansfield, Ivan Diakonov, Aleksandra Judina, Matthew Delahaye, Navneet Bhogal, Jose L Sanchez-Alonso, Timothy Kamp, Julia Gorelik","doi":"10.1093/cvr/cvae265","DOIUrl":"10.1093/cvr/cvae265","url":null,"abstract":"<p><strong>Aims: </strong>Caveolin-3 is essential for the formation of caveolae in cardiomyocytes. Caveolar microdomains have been shown to regulate the distribution of signalling proteins such as beta-adrenoceptors (βAR) and may act as membrane reserves to protect the cell from damage during the mechanical stretch. Myocardial stretch occurs during haemodynamic overload and may be normal (e.g. exercise) or pathological (e.g. heart failure); therefore, it is important to understand the effect of stretch on signalling pathways associated with mechanosensitive structures, such as caveolae. In this study, we investigate the role of caveolae in regulating the effect of stretch on βAR-signalling.</p><p><strong>Methods and results: </strong>We used osmotic swelling of isolated rat ventricular cardiomyocytes as a method to stretch the cell membrane and investigate the effect of βAR stimulation on cyclic adenosine monophosphate (cAMP) activity and contractility. βAR response was measured using a Förster Resonance Energy Transfer reporter for the second messenger cAMP and using CytoCypher for the measurement of cell contractility. β1AR and β2AR blockers were used to selectively allow stimulation of β2AR and β1AR, respectively. We also investigated the effect of stretch on βAR response to isoprenaline stimulation in left ventricular trabeculae dissected from control and cardiac-specific caveolin-3 knock-out mice (Cav3KO). Stretching trabeculae produces increased baseline adenylyl cyclase activity and a higher level of cAMP and a greater β2AR-induced positive inotropy after stimulation of the β2AR but not β1AR, by isoprenaline. Similar findings were confirmed for isolated myocytes subjected to hypoosmotic conditions. In isolated cardiomyocytes, caveolae depletion using methyl-beta-cyclodextrin or Cav3KO abolished the increase in β2AR response induced by stretch.</p><p><strong>Conclusion: </strong>Our study reveals a stretch-regulation of the β2AR signalling pathway, which requires functional caveolae. This indicates caveolae are mechanosensitive membrane domains that undergo structural and functional changes in response to stretch, thus leading to mechanical regulation of caveolae-associated signalling pathways.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"440-453"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vasoconstriction-inhibiting factor: an endogenous inhibitor of vascular calcification as a calcimimetic of calcium-sensing receptor.","authors":"Sofía de la Puente-Secades, Dustin Mikolajetz, Nathalie Gayrard, Juliane Hermann, Vera Jankowski, Shruti Bhargava, Amina Meyer, Àngel Argilés, Turgay Saritas, Emiel P C van der Vorst, Zhuojun Wu, Heidi Noels, Martin Tepel, Khaleda Alghamdi, Donald Ward, Walter Zidek, Michael Wolf, Jürgen Floege, Leon Schurgers, Setareh Orth-Alampour, Joachim Jankowski","doi":"10.1093/cvr/cvaf016","DOIUrl":"10.1093/cvr/cvaf016","url":null,"abstract":"<p><strong>Aims: </strong>Patients with chronic kidney disease (CKD) show a high risk of cardiovascular diseases, predominantly caused by accelerated vascular calcification. Vascular calcification is a highly regulated process with no current treatment. The vasoconstriction-inhibiting factor (VIF) peptide was recently discovered with vasoregulatory properties, but no information regarding calcification has been described.</p><p><strong>Methods and results: </strong>In the present work, the inhibitory calcification effect of the VIF peptide was analysed in vitro in vascular smooth muscle cells (VSMCs), ex vivo in rat aortic rings, as well as in vivo in rats treated with vitamin D and nicotine (VDN). The VIF peptide inhibits vascular calcification by acting as a calcimimetic for the calcium-sensing receptor, increasing carboxylated matrix Gla protein production and blocking the activation of calcification pathways. The VIF peptide decreased calcium influx, the production of reactive oxygen species, and the activation of multiple kinases in VSMCs. Furthermore, calcium deposition in the aortas of patients with CKD negatively correlates with the VIF peptide concentration. Moreover, we show the cleavage of the VIF peptide from chromogranin-A by 'proprotein convertase subtilisin/kexin type 2' and 'carboxypeptidase E' enzymes. In addition, 'cathepsin K' degrades the VIF peptide. The active site of the native 35 amino acid-sequence long VIF peptide was identified with seven amino acids, constituting a promising drug candidate with promise for clinical translation.</p><p><strong>Conclusion: </strong>The elucidation of the underlying mechanism by which the VIF peptide inhibits vascular calcification, as well as the active sequence and the cleavage and degradation enzymes, forms the basis for developing preventive and therapeutic measures to counteract vascular calcification.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"507-521"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical coherence tomography assessment of the impact of colchicine on non-culprit coronary plaque composition after myocardial infarction.","authors":"Peter J Psaltis, Mau T Nguyen, Kuljit Singh, Ajay Sinhal, Dennis T L Wong, Richard Alcock, Sharmalar Rajendran, Rustem Dautov, Peter Barlis, Sanjay Patel, Thalia Salagaras, Jessica A Marathe, Christina A Bursill, Nicholas J Montarello, Stefan M Nidorf, Peter L Thompson, Julie Butters, Alana R Cuthbert, Lisa N Yelland, Juanita L Ottaway, Yu Kataoka, Giuseppe Di Giovanni, Stephen J Nicholls","doi":"10.1093/cvr/cvae191","DOIUrl":"10.1093/cvr/cvae191","url":null,"abstract":"<p><strong>Aims: </strong>Low-dose colchicine reduces the risk of cardiovascular events after myocardial infarction (MI). The purpose of this study was to assess the effect of colchicine post-MI on coronary plaque morphology in non-culprit segments by optical coherence tomography (OCT).</p><p><strong>Methods and results: </strong>COCOMO-ACS was a double-blind, placebo-controlled trial that randomized 64 patients (median age 61.5 years; 9.4% female) with acute non-ST-segment elevation MI to colchicine 0.5 mg daily or placebo for a median of 17.8 months in addition to guideline-recommended therapy. Participants underwent serial OCT imaging within a matched segment of non-culprit coronary artery that contained at least one lipid-rich plaque causing ≥20% stenosis. The primary outcome was the change in minimum fibrous cap thickness (FCT) in non-culprit segments from baseline to final visit. Of those randomized, 57 (29 placebo, 28 colchicine) had evaluable imaging at baseline and follow-up. Overall, colchicine had no effect on relative (placebo +48.0 ± 35.1% vs. colchicine +62.4 ± 38.1%, P = 0.18) or absolute changes in minimum FCT (+29.2 ± 20.9 µm vs. + 37.2 ± 21.3 µm, P = 0.18), or change in maximum lipid arc (-38.8 ± 32.2° vs. -54.8 ± 46.9°, P = 0.18) throughout the imaged non-culprit segment. However, in patients assigned colchicine, cap rupture was less frequent (placebo 27.6% vs. colchicine 3.6%, P = 0.03). In post hoc analysis of 43 participants who had been followed for at least 16 months, minimum FCT increased to a greater extent in the colchicine group (placebo +38.7 ± 25.4% vs. colchicine +64.7 ± 34.1%, P = 0.005).</p><p><strong>Conclusion: </strong>In this study, OCT failed to detect an effect of colchicine on the minimum FCT or maximum lipid arc of plaques in non-culprit segments post-MI. The post hoc observation that minimum FCT increased to a greater extent with colchicine after more prolonged treatment suggests that longer-term studies may be required to detect the effect of anti-inflammatory therapies on plaque morphology by OCT.</p><p><strong>Clinical trial number: </strong>Australian New Zealand Clinical Trials Registry Identifier, ACTRN12618000809235, registered on the 11 May 2018.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"468-478"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell RNA sequencing of haematopoietic cells in fresh and frozen human atheroma tissue.","authors":"Herra Ahmad, Jayakrishnan Gopakumar, Daniel C Nachun, Lisa Ma, Jessica D'Addabbo, Xianxi Huang, Tiffany Koyano, Jack Boyd, Yi-Ping Joseph Woo, Robyn Fong, Oliver Aalami, Patricia K Nguyen, Siddhartha Jaiswal","doi":"10.1093/cvr/cvaf014","DOIUrl":"10.1093/cvr/cvaf014","url":null,"abstract":"<p><strong>Aims: </strong>Single-cell RNA sequencing (scRNA-seq) is a powerful method for exploring the cellular heterogeneity within human atheroma but typically requires fresh tissue to preserve cell membrane integrity, limiting the feasibility of large-scale biobanking for later analysis. The aim of this study was to determine whether cryopreservation of fragile and necrotic atheroma tissue affects the viability and transcriptomic profiles of haematopoietic cells in subsequent scRNA-seq analysis, enabling the use of cryopreserved atheroma samples for future research.</p><p><strong>Methods and results: </strong>We performed scRNA-seq on five paired fresh and cryopreserved atheroma samples-three from coronary arteries and two from carotid arteries. Each sample was enzymatically digested, sorted for CD45+ haematopoietic cells, and processed using the 10× Genomics scRNA-seq workflow. Half of each sample was processed immediately, while the other half was cryopreserved in liquid nitrogen for an average of 5 weeks before thawing and processing. In carotid artery samples, we noted the absence of LYVE1+ macrophages, likely due to the loss of the adventitial layer during endarterectomy procedures. Our results indicated that cryopreservation modestly affected cellular integrity, leading to an increase in the relative abundance of mitochondrial RNA in frozen samples. Minimal differences were observed between fresh and cryopreserved samples in uniquely detected transcripts, cell clustering, or transcriptional profiles within haematopoietic populations.</p><p><strong>Conclusions: </strong>Our study demonstrates that cryopreserved human atheroma samples can be successfully profiled using scRNA-seq, with comparable transcriptomic data to that obtained from fresh samples. These findings suggest that cryopreservation is a viable method for biobanking atheroma tissues, facilitating large-scale studies without the need for immediate sample processing.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"396-404"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colchicine and stabilization of coronary artery plaques.","authors":"Valtteri Muroke, Jean-Claude Tardif","doi":"10.1093/cvr/cvaf019","DOIUrl":"10.1093/cvr/cvaf019","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"374-375"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abdominal aortic aneurysm histomorphology shows different inflammatory aspects among patients and is not associated with classic risk factors – the HistAAA study","authors":"Maja Carina Nackenhorst, Felix Menges, Bianca Bohmann, David Zschäpitz, Christine Bollwein, Sven Flemming, Nadja Sachs, Wolf Eilenberg, Christine Brostjan, Christoph Neumayer, Matthias Trenner, Wiebke Ibing, Hubert Schelzig, Christian Reeps, Lars Maegdefessel, Heinz Regele, Markus Udo Wagenhäuser, Claus Jürgen Scholz, Thomas Christian Gasser, Albert Busch","doi":"10.1093/cvr/cvaf071","DOIUrl":"https://doi.org/10.1093/cvr/cvaf071","url":null,"abstract":"Text Abstract Aims Abdominal aortic aneurysm (AAA) treatment is upon a diameter threshold. Attempts for medical growth abrogation have failed thus far. This study aims to elucidate the heterogeneity of AAA histomorphology in correlation to individual patient and aneurysm metrics. Methods and Results Samples from the left anterior aneurysm wall underwent histologic analysis including angiogenesis, calcification, fibrosis, type and grade of inflammation in adventitia and media. Clinical information and state of aneurysm (intact, symptomatic, ruptured, inflammatory) were retrieved. Semi-automated geometric analysis (Endosize©, Therenva) and finite element methods (A4Clinics© Research Edition, Vascops GmbH) were included. 364 patients’ samples (85.4% male, median age 69 years) were scored for acute or chronic inflammation, both not associated with rupture (52x), symptomatic disease (37x) or diameter (57 [52-69] mm; p = 0.87). The degree of fibrosis and the presence of angiogenesis were significantly higher (both p &amp;lt; 0.001) with increasing inflammation, which in turn significantly decreased with patient age (est = - 0.015/year, p = 0.017). No significant differences were seen for acute (vs. elective), male (vs. female) or diabetic patients. Aneurysm geometry (n=252) or annual growth rate (n=142) were not associated with histologic characteristics. Yet, local luminal thrombus formation was significantly higher with increasing inflammation (p = 0.04). Conclusion Type and degree of inflammation are the most distinguishable histologic characteristics in the AAA wall between individual patients, yet are not associated with diameter or rupture. Local luminal thrombus formation is associated with inflammatory features and suggests a vivid bio-physical compartment with intra-individual age-dependent differences.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"140 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct intracellular spatiotemporal expression of Calmodulin genes underlies functional diversity of CaM-dependent signaling in cardiac myocytes","authors":"Vladimir Bogdanov, Juan I E Mariangelo, Andrew M Soltisz, Galina Sakuta, Anastasia Pokrass, Casey Beard, Benjamin Hernandez Orengo, Roman Kalinin, Ali Ulker, Bennett Yunker, Svetlana Tikunova, Jenna Thuma, Xianyao Xu, Thomas J Hund, Rengasayee Veeraraghavan, Jonathan P Davis, Sandor Györke","doi":"10.1093/cvr/cvaf059","DOIUrl":"https://doi.org/10.1093/cvr/cvaf059","url":null,"abstract":"Aims This study aims to resolve the mechanisms underlying Calmodulin (CaM)'s signaling diversity by investigating whether the three CaM genes—Calm1, Calm2, and Calm3—play distinct or redundant roles in cardiac myocytes, focusing on their spatial mRNA localization and interactions with key targets. Methods and Results We utilized single-molecule mRNA detection and 3D imaging to map the spatial distribution of Calm1, Calm2, and Calm3 mRNAs within ventricular myocytes. These mRNAs were found to be consistently positioned within specific cellular zones, overlapping with their target mRNAs and forming region-specific transcript conjunctions. This spatial organization aligns with two distinct protein synthesis pathways: centralized synthesis near the nucleus for proteins such as Cx43 and localized synthesis in more peripheral cytosolic areas for proteins like RyR2. Ablation of Calm1 triggered compensatory increases in Calm2 and Calm3; however, this compensation was insufficient to restore normal CaM transcript distribution, leading to disrupted Ca²⁺ handling. In the context of hypertrophic heart failure (HF), the distribution and spatial interactions of CaM transcripts, while potentially adaptive to support myocyte growth, become disrupted, leading to disorganized CaM signaling. Conclusion Our findings reveal that Calm1, Calm2, and Calm3 fulfill distinct, non-redundant roles in cardiac myocytes through their spatially regulated mRNA localization (spatiotemporal coding). This precise spatial control of mRNA localization is critical for region-specific CaM signaling and is disrupted in hypertrophic heart failure, contributing to pathological remodeling.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"2 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new protein isoform encoded by human circular RNA circSLC8a1 contributes to cardiac remodeling","authors":"Feiya Li, William W Du, Xiangmin Li, Shuoyang Wen, Jindong Xu, Qiwei Yang, Jinfeng Wei, Sheng Wang, Nan Wu, Javeria Qadir, Burton B Yang","doi":"10.1093/cvr/cvaf058","DOIUrl":"https://doi.org/10.1093/cvr/cvaf058","url":null,"abstract":"Aims Circular RNA circSLC8a1 has been previously suggested to possess translation potential, but experimental evidence supporting this notion has been lacking. We aim to understand the functions of circSLC8a1 and its translated protein in cardiac remodeling. Methods and Results To elucidate the functional significance of circSLC8a1, we established a transgenic mouse line expressing circSLC8a1 and its translated protein SLC8a1-604. We present compelling evidence confirming the translation potential of circSLC8a1 (hsa_circ_0005232) both in vitro and in vivo. The back-splicing event within hsa_circ_0005232 leads to the generation of a novel circRNA-derived protein comprising 604 amino acids, named SLC8a1-604, which has not been previously reported. These SLC8a1-604 transgenic mice exhibited a heart failure phenotype. In further investigations, we induced pressure overload in the transgenic mice, revealing a significant decrease in heart function compared to litter-matched negative controls. Notably, our findings indicate that the reduced heart function observed in the transgenic mice can be attributed to the presence of the circRNA-translated protein, SLC8a1-604, rather than the circRNA itself. Mechanistically, we found that SLC8a1-604 translocated into mitochondria, where it exerted its effects by binding to POLRMT. This interaction results in a downregulation of mitochondrial gene transcription, leading to a decrease in ATP synthesis. Conclusion Our study provides evidence that circSLC8a1 has the capacity to encode a novel protein isoform, SLC8a1-604, which plays a pivotal role in the regulation of heart functions: circSLC8a1 modulates the remodeling process of cardiac pressure overload by translating into a functional protein. Translational Perspective This proof-of-concept study may lay the foundation for potential clinical applications in circular RNA therapy.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"17 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and sex hormonal regulation of the atrial inward rectifier potassium current (IK1): insights into potential pro-arrhythmic mechanisms.","authors":"Lucilla Giammarino,Lluis Matas,Nicolò Alerni,András Horváth,Varjany Vashanthakumar,Saranda Nimani,Miriam Barbieri,Sahej Bains,Ruben Lopez,Julien Louradour,Balazs Ördög,Thomas Hof,Ange Maguy,Giulio Conte,Angelo Auricchio,Ulrich Schotten,Katja E Odening","doi":"10.1093/cvr/cvaf074","DOIUrl":"https://doi.org/10.1093/cvr/cvaf074","url":null,"abstract":"AIMSPronounced sex-differences are known in the incidence of atrial fibrillation (AF). In this study, we aimed to investigate the atrial electrophysiological properties that may underlie sex-differences in AF incidence in the younger population, focusing on IK1, a cardiac ion current important for action potential (AP) stability and triggered activity.METHODS AND RESULTSWe assessed sex-differences in P-wave morphology in 12-lead ECG in healthy young New Zealand White rabbits. Males presented longer P-wave duration and larger P-wave area compared to females. Patch-clamp experiments were performed in isolated rabbit atrial cardiomyocytes (CMs). Male atrial CMs presented higher DAD incidence, amplitude, and area under the curve (AUC) than females, potentially facilitating the presence of atrial triggered activity in males. Male atrial CMs showed a less hyperpolarized resting membrane potential (RMP), a 50% smaller IK1, and a 26% reduction in Kir2.1 protein expression, a pore forming subunit of IK1, than females. Dihydrotestosterone (DHT) effects were investigated acutely and semi-chronically ex vivo. Experiments showed that the sex-difference in IK1 could be mimicked by DHT. In female atrial CMs, acute and semi-chronic (24h) DHT administration reduced IK1. In the presence of a PKC-inhibitor, DHT-mediated IK1 reduction was not observed in atrial female CMs, suggesting it to be PKC-mediated. Chronic DHT-effects were investigated in vivo in female rabbits after hormone-releasing pellet implantation. After two weeks, animals showed a significantly prolonged and larger P-wave, a smaller atrial IK1 and a trend towards an increased DAD amplitude and AUC.CONCLUSIONSSex impacts on atrial electrophysiology, leading to sex-differences in P-wave morphology, triggered activity, RMP, and IK1. These sex-differences can be mimicked by sex hormone-treatment, suggesting that sex hormones ‒ particularly DHT ‒ play a pivotal role in mediating sex-differences in atrial electrophysiology. Such sex-differences might impact on the propensity to develop AF, particularly in the younger population.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"5 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of pulmonary artery stiffening due to left heart disease by ultrasonography","authors":"Mariya M Kucherenko, Marian Kukucka, Pengchao Sang, Niklas Hegemann, Qiuhua Li, Felix Hennig, Ruhi Yeter, Tara Gransar, Alexander Mladenow, Anna Emmerich, Andrea Orsenigo, Jana Grune, Volkmar Falk, Wolfgang M Kuebler, Christoph Knosalla","doi":"10.1093/cvr/cvaf066","DOIUrl":"https://doi.org/10.1093/cvr/cvaf066","url":null,"abstract":"Aims Pulmonary hypertension (PH) is a common complication of left heart disease (LHD) that leads to right heart failure and death. Pulmonary artery (PA) stiffening has recently emerged as an important diagnostic and prognostic parameter in PH. The present study aimed to develop and validate an ultrasonographic index to identify PA stiffening in PH due to left heart disease (PH-LHD). Methods and Results First, ultrasonographic stiffness index (US-SI) was derived from pulmonary arterial (PA) radial strain (PA-RS), diameter, and stroke volume in rat model, and correlated to ex vivo measured “true” PA stiffness E. Then, US-SI was validated in a cohort of 24 LHD patients with or without PH prior to heart transplantation and again compared to “true” PA stiffness measured ex vivo in collected PA specimens. In rats, ultrasonographic PA-RS and US-SI correlated closely with E, and both were able to detect “true” PA stiffening with ≥ 80% sensitivity and specificity. In LHD patients, even though ultrasonographic right PA radial strain (rPA-RS) or US-SI correlated similarly with E, observer assessment and testing for diagnostic validity identified US-SI as more robust and accurate method that detects “true” PA stiffening with 83.3% sensitivity and 95.8% specificity. Conclusion(s) Both PA strain and US-SI allow for ultrasonographic detection of PA stiffening in patients or animal models with LHD, however, US-SI identifies patients with stiffened PA with higher diagnostic validity and accuracy. Translational Perspective Clinical implementation of US-SI may improve risk stratification in LHD patients and longitudinal monitoring of progression or treatment efficiency in PH-LHD. The animal-to-beside approach used in this study may promote the rapid translation of bio- and pathomechanical insights between the clinical and preclinical scenarios.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"1 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}