Translational Cardiovascular Research Research Articles

Dynamic Narrowing of the Diaphragmatic Vena Cava in Ovis aries.

Dorset sheep (Ovis aries) are common models in translational cardiovascular research due to physiologic and anatomic similarities to humans. While employing ovine subjects to study single-ventricle physiology, we repeatedly observed position-based changes in central venous pressure (CVP) which could not be explained by hydrostatic (gravitational) effects. Inferior vena cava (IVC) narrowing or compression has been demonstrated in numerous species, and we hypothesised that this phenomenon might explain our observations in O. aries. This study aimed to characterise position-dependent morphology of the IVC in O. aries using catheter-based hemodynamic and dimensional measurements, three-dimensional MRI reconstruction and histological analysis. Baseline measurements revealed a significant reduction in IVC dimensions at the level of the diaphragm (dVC) compared to the abdominal vena cava (aVC) and thoracic vena cava (tVC). We also observed a transdiaphragmatic pressure gradient along the IVC, with higher pressures in the aVC compared to the tVC. We found that variation of position and fluid status altered IVC haemodynamics. Histological data showed variable muscularity along the length of the IVC, with greater smooth muscle content in the aVC than the tVC. These findings will improve understanding of baseline ovine physiology, help refine experimental protocols and facilitate the translation of findings to the clinic.

A gender perspective on diet, microbiome, and sex hormone interplay in cardiovascular disease.

A unique interplay between body and environment embeds and reflects host-microbiome interactions that contribute to sex-differential disease susceptibility, symptomatology, and treatment outcomes. These differences derive from individual biological factors, such as sex hormone action, sex-divergent immune processes, X-linked gene dosage effects, and epigenetics, as well as from their interaction across the lifespan. The gut microbiome is increasingly recognized as a moderator of several body systems that are thus impacted by its function and composition. In humans, biological sex components further interact with gender-specific exposures such as dietary preferences, stressors, and life experiences to form a complex whole, requiring innovative methodologies to disentangle. Here, we summarize current knowledge of the interactions among sex hormones, gut microbiota, immune system, and vascular health and their relevance for sex-differential epidemiology of cardiovascular diseases. We outline clinical implications, identify knowledge gaps, and place emphasis on required future studies to address these gaps. In addition, we provide an overview of the caveats associated with conducting cardiovascular research that require consideration of sex/gender differences. While previous work has inspected several of these components separately, here we call attention to further translational utility of a combined perspective from cardiovascular translational research, gender medicine, and microbiome systems biology.

Comparison effect of high-intensity interval training and moderate intensity continuous training on vascular function in a mouse model of lower extremity peripheral artery disease

Introduction
 Lower extremity peripheral artery disease (PAD), due to narrowing of the arteries supplying the legs, represents a major cause of physical disability. Exercise training is an important part of PAD treatment, improving functional capacity. Recent research suggests that exercise training-induced endothelial function improvement is involved in the benefits of exercise in PAD (Lee et al., 2023); however, the underlying molecular mechanisms remain unknown. In addition, the potential vascular benefits of high intensity training in PAD remain unexplored. Therefore, the aim of the study was to compare the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on endurance capacity, vascular endothelial function and expression of genes related to nitric oxide (NO) bioavailability in a mouse model of PAD.
 Methods
 PAD disease model was generated in male C57BL/6 mice by ligation of the right iliac artery. Mice with PAD were divided into 3 groups: sedentary control group (SED), MICT (40 min running at 70% of maximal aerobic speed) and HIIT (8 intervals of 2.5 minutes running at 90% of maximal aerobic speed combined with 2.5 minutes of running at 50% of maximal aerobic speed). Mice were exercised three times per week for 8 weeks. Maximal running time was determined by an incremental test until exhaustion. Vascular reactivity was assessed by measuring vasoconstrictor responses to phenylephrine as well as endothelium-dependent and -independent vasodilator responses to acetylcholine and DEA-NONOate, respectively, in isolated aortic rings. Gene expression of antioxidant enzymes (catalase and superoxide dismutase isoforms), prooxidant NADPH oxidase subunits (p22phox and p47phox), enzyme involved in NO production (endothelial NO synthase), vascular smooth muscle cell relaxation (soluble guanylate cyclase) and receptors involved in vascular tone regulation (a1 and b2 adrenergic receptors) was determined in aortic tissue by qPCR.
 Results
 Maximal running time was improved in both MICT and HIIT as compared to SED at the end of the study, but with no significant difference between the two exercise groups. Phenylephrine-induced vasoconstriction as well as vasodilator responses to acetylcholine and DEA-NONOate were significantly improved in MICT compared to SED while no significant differences were reported between HIIT and SED. There was no significant difference in gene expression among the three groups.
 Discussion/Conclusion
 MICT and HIIT were equally effective at improving endurance capacity in mice with PAD. However, only MICT improved vascular reactivity.
 References
 Lee, J., Zarezadehmehrizi, A., LaVoy, E., Markofski, M., & Park, Y. (2023). Exercise training improves brachial artery endothelial function, but does not alter inflammatory biomarkers in patients with peripheral artery disease: A systematic review and meta-analysis. Journal of Cardiovascular Translational Research. Advance online publication. https://doi.org/10.1007/s12265-023-10451-0

Current status of cardiovascular translational medicine research: from high throughput multi omics to integrative bioinformatics

Current status of cardiovascular translational medicine research: from high throughput multi omics to integrative bioinformatics

Profiling the Biomechanical Responses to Workload on the Human Myocyte to Explore the Concept of Myocardial Fatigue and Reversibility: Rationale and Design of the POWER Heart Failure Study.

It remains unclear why some patients develop heart failure without evidence of structural damage. One theory relates to impaired myocardial energetics and ventricular-arterial decoupling as the heart works against adverse mechanical load. In this original study, we propose the novel concept of myocardial fatigue to capture this phenomenon and aim to investigate this using human cardiomyocytes subjected to a modern work-loop contractility model that closely mimics in vivo cardiac cycles. This proof-of-concept study (NCT04899635) will use human myocardial tissue samples from patients undergoing cardiac surgery to develop a reproducible protocol to isolate robust calcium-tolerant cardiomyocytes. Thereafter, work-loop contractility experiments will be performed over a range of preload, afterload and cycle frequency as a function of time to elicit any reversible reduction in contractile performance (i.e. fatigue). This will provide novel insight into mechanisms behind heart failure and myocardial recovery and serve as a valuable research platform in translational cardiovascular research.

Developing informatics infrastructure to curate datasets using electronic health record data from five hospitals for translational cardiovascular research

Abstract Introduction It has been challenging for researchers to access granular electronic health record (EHR) data at scale. One emerging prospect is to use big data to traverse the translational spectrum from an early discovery phase to a later implementation phase. Purpose To create a research-ready dataset to support translational research in cardiovascular medicine, using routinely-collected EHR data from multiple hospitals. As an early discovery phase study, we estimated the effect of invasive versus non-invasive management on the survival of patients with non-ST elevation myocardial infarction (NSTEMI) aged 80 years or older (SENIOR-NSTEMI Study). As a later implementation phase study, we determined the relationship between the full spectrum of troponin level and mortality in patients in whom troponin testing was performed for clinical purposes (TROP-RISK Study). Methods Using Microsoft SQL we developed a dataset of 257948 consecutive patients who had a troponin measured between 2010 and 2017 at five hospitals. We extracted phenotypically detailed data, including demographics, blood tests, procedural data, and survival status. For the SENIOR-NSTEMI Study, eligible patients were 80 years or older who were diagnosed with NSTEMI. We estimated mortality hazard ratios comparing invasive with non-invasive management. For the TROP-RISK Study, we modelled the relation between peak troponin level and all-cause mortality using multivariable adjusted restricted cubic spline Cox regression analyses. Results For the SENIOR-NSTEMI Study, 1500 patients with NSTEMI were included who had a median age of 86 (interquartile range (IQR) 82–89) years of whom (845 [56%]) received non-invasive management. During a median follow-up of 3 (IQR 1.2–4.8) years, the adjusted cumulative five-year mortality was 36% in the invasive and 55% in the non-invasive group (hazard ratio 0.68, 95% confidence interval 0.55–0.84). For the TROP-RISK Study, during a median follow-up of 1198 days (IQR 514–1866 days), 55850 (21.7%) deaths occurred. There was an unexpected inverted U-shaped relation between troponin level and mortality in acute coronary syndrome (ACS) patients (n=120049) (Figure 1A). The paradoxical decline in mortality at very high troponin levels may be driven in part by the changing case mix as troponin levels increase; a higher proportion of patients with very high troponin levels received invasive management (Figure 1B). Conclusion Routine EHR data can be aggregated across multiple sites to create highly granular datasets for research. The SENIOR-NSTEMI Study showed a survival advantage of invasive compared with non-invasive management of elderly patients with NSTEMI, who were underrepresented in previous trials. The inverted U-shaped relationship between troponin and mortality in ACS patients in the TROP-RISK Study demonstrates that assembling sufficiently large datasets can cast light on patterns of disease that are impossible to adequately define in single centre studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1) NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative, and 2) British Heart Foundation

RBPMS2 Is a Myocardial-Enriched Splicing Regulator Required for Cardiac Function.

RBPs (RNA-binding proteins) perform indispensable functions in the post-transcriptional regulation of gene expression. Numerous RBPs have been implicated in cardiac development or physiology based on gene knockout studies and the identification of pathogenic RBP gene mutations in monogenic heart disorders. The discovery and characterization of additional RBPs performing indispensable functions in the heart will advance basic and translational cardiovascular research. We performed a differential expression screen in zebrafish embryos to identify genes enriched in nkx2.5-positive cardiomyocytes or cardiopharyngeal progenitors compared to nkx2.5-negative cells from the same embryos. We investigated the myocardial-enriched gene RNA-binding protein with multiple splicing (variants) 2 [RBPMS2)] by generating and characterizing rbpms2 knockout zebrafish and human cardiomyocytes derived from RBPMS2-deficient induced pluripotent stem cells. We identified 1848 genes enriched in the nkx2.5-positive population. Among the most highly enriched genes, most with well-established functions in the heart, we discovered the ohnologs rbpms2a and rbpms2b, which encode an evolutionarily conserved RBP. Rbpms2 localizes selectively to cardiomyocytes during zebrafish heart development and strong cardiomyocyte expression persists into adulthood. Rbpms2-deficient embryos suffer from early cardiac dysfunction characterized by reduced ejection fraction. The functional deficit is accompanied by myofibril disarray, altered calcium handling, and differential alternative splicing events in mutant cardiomyocytes. These phenotypes are also observed in RBPMS2-deficient human cardiomyocytes, indicative of conserved molecular and cellular function. RNA-sequencing and comparative analysis of genes mis-spliced in RBPMS2-deficient zebrafish and human cardiomyocytes uncovered a conserved network of 29 ortholog pairs that require RBPMS2 for alternative splicing regulation, including RBFOX2, SLC8A1, and MYBPC3. Our study identifies RBPMS2 as a conserved regulator of alternative splicing, myofibrillar organization, and calcium handling in zebrafish and human cardiomyocytes.

At the forefront of basic and translational Cardiovascular Research for 55 years and counting.

At the forefront of basic and translational Cardiovascular Research for 55 years and counting.

Developing informatics infrastructure to curate datasets using electronic health record data from five hospitals for translational cardiovascular research

Abstract Introduction It has been challenging for researchers to access granular electronic health record (EHR) data at scale. One emerging prospect is to use big data to traverse the translational spectrum from an early discovery phase to a later implementation phase. Purpose To create a research-ready dataset to support translational research in cardiovascular medicine, using routinely-collected EHR data from multiple hospitals. As an early discovery phase study, we estimated the effect of invasive versus non-invasive management on the survival of patients with non-ST elevation myocardial infarction (NSTEMI) aged 80 years or older (SENIOR-NSTEMI Study). As a later implementation phase study, we determined the relationship between the full spectrum of troponin level and mortality in patients in whom troponin testing was performed for clinical purposes (TROP-RISK Study). Methods Using Microsoft SQL we developed a dataset of 257948 consecutive patients who had a troponin measured between 2010 and 2017 at five hospitals. We extracted phenotypically detailed data, including demographics, blood tests, procedural data, and survival status. For the SENIOR-NSTEMI Study, eligible patients were 80 years or older who were diagnosed with NSTEMI. We estimated mortality hazard ratios comparing invasive with non-invasive management. For the TROP-RISK Study, we modelled the relation between peak troponin level and all-cause mortality using multivariable adjusted restricted cubic spline Cox regression analyses. Results For the SENIOR-NSTEMI Study, 1500 patients with NSTEMI were included who had a median age of 86 (interquartile range (IQR) 82–89) years of whom (845 [56%]) received non-invasive management. During a median follow-up of 3 (IQR 1.2–4.8) years, the adjusted cumulative five-year mortality was 36% in the invasive and 55% in the non-invasive group (hazard ratio 0.68, 95% confidence interval 0.55–0.84). For the TROP-RISK Study, during a median follow-up of 1198 days (IQR 514–1866 days), 55850 (21.7%) deaths occurred. There was an unexpected inverted U-shaped relation between troponin level and mortality in acute coronary syndrome (ACS) patients (n=120049) (Figure 1A). The paradoxical decline in mortality at very high troponin levels may be driven in part by the changing case mix as troponin levels increase; a higher proportion of patients with very high troponin levels received invasive management (Figure 1B). Conclusion Routine EHR data can be aggregated across multiple sites to create highly granular datasets for research. The SENIOR-NSTEMI Study showed a survival advantage of invasive compared with non-invasive management of elderly patients with NSTEMI, who were underrepresented in previous trials. The inverted U-shaped relationship between troponin and mortality in ACS patients in the TROP-RISK Study demonstrates that assembling sufficiently large datasets can cast light on patterns of disease that are impossible to adequately define in single centre studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1) NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative, and 2) British Heart Foundation

Raymond A Dieter, Jr. MD MS

Raymond A Dieter, Jr. MD MS

Current Status and Limitations of Myocardial Infarction Large Animal Models in Cardiovascular Translational Research.

Establishing an appropriate disease model that mimics the complexities of human cardiovascular disease is critical for evaluating the clinical efficacy and translation success. The multifaceted and complex nature of human ischemic heart disease is difficult to recapitulate in animal models. This difficulty is often compounded by the methodological biases introduced in animal studies. Considerable variations across animal species, modifications made in surgical procedures, and inadequate randomization, sample size calculation, blinding, and heterogeneity of animal models used often produce preclinical cardiovascular research that looks promising but is irreproducible and not translatable. Moreover, many published papers are not transparent enough for other investigators to verify the feasibility of the studies and the therapeutics’ efficacy. Unfortunately, successful translation of these innovative therapies in such a closed and biased research is difficult. This review discusses some challenges in current preclinical myocardial infarction research, focusing on the following three major inhibitors for its successful translation: Inappropriate disease model, frequent modifications to surgical procedures, and insufficient reporting transparency.

Tackling prosthetic heart valve-related deterioration: Liège translational cardiovascular research programme.

Tackling prosthetic heart valve-related deterioration: Liège translational cardiovascular research programme.

Living myocardial slices: a novel multicellular model for cardiac translational research.

Heart function relies on the interplay of several specialized cell types and a precisely regulated network of chemical and mechanical stimuli. Over the last few decades, this complexity has often been undervalued and progress in translational cardiovascular research has been significantly hindered by the lack of appropriate research models. The data collected are often oversimplified and these make the translation of results from the laboratory to clinical trials challenging and occasionally misleading. Living myocardial slices are ultrathin (100–400μm) sections of living cardiac tissue that maintain the native multicellularity, architecture, and structure of the heart and can provide information at a cellular/subcellular level. They overcome most of the limitations that affect other in vitro models and they can be prepared from human specimens, proving a clinically relevant multicellular human model for translational cardiovascular research. The publication of a reproducible protocol, and the rapid progress in methodological and technological discoveries which prevent significant structural and functional changes associated with chronic in vitro culture, has overcome the last barrier for the in vitro use of this human multicellular preparations. This technology can bridge the gap between in vitro and in vivo human studies and has the potential to revolutionize translational research approaches.

Basic Cardiovascular Sciences Scientific Sessions 2019: Integrative Approaches to Complex Cardiovascular Diseases.

The annual Basic Cardiovascular Sciences (BCVS) Scientific Sessions remains a premier conference destination for those in the basic and translational cardiovascular research community. This year’s BCVS meeting was held at the downtown waterfront in Boston, MA from July 29 to August 1, 2019. To say that BCVS 2019 was well-attended is truly an understatement, as this year’s meeting broke all BCVS conference records with over 1000 registered attendees, over 600 posters, and a plethora of new offerings, such as expanded early career sessions and the first Asian Cardiovascular Symposium. Here, we highlight some of the emerging science and exciting programming that was featured at the 2019 BCVS Scientific Sessions.

Association between Daytime Sleepiness and Cardiometabolic Risk Factors

BackgroundSleep disturbances are increasingly common and associated with adverse health outcomes. Inadequate sleep may also produce daytime symptoms, such as excessive sleepiness. Growing research identifies daytime sleepiness as a risk factor for morbidity and mortality. However, it is unclear whether these associations are independent of the presence of sleep disordered breathing, a primary cause of hypersomnolence.ObjectiveIn this study, we sought to assess the relation between daytime sleepiness and established cardiometabolic risk factors, independently of obstructive sleep apnea.MethodsWe compiled data from 456 individuals (69% male, age 51.3±15.7 years) who participated in research studies performed in the Cardiovascular/Sleep Laboratory at Mayo Clinic and had complete sleepiness data. Height and weight were measured to calculate body mass index (BMI, kg/m2). Obesity was defined as BMI ≥30 kg/m2. Hypertension was determined as self‐reported diagnosis or taking antihypertensive medications. Diabetes mellitus was defined as patient‐reported diabetes or usage of insulin or antidiabetic drugs. Obstructive sleep apnea (OSA) was self‐reported or determined from polysomnography. Subjective daytime sleepiness was defined as an affirmative answer to the question “Are you usually sleepy during the daytime?”.ResultsDaytime sleepiness was reported by 51% of the subjects (n=231). Those with daytime sleepiness were more likely to be male (74.9% vs 62.3%, P=0.005), but the average age was similar between groups (51.6±17.3 years vs 51±14.1 years, P=0.67). BMI was greater among the subjects with perceived daytime sleepiness than in those without (32.2±7 kg/m2 vs 28.9±6.8 kg/m2, P<0.0001), and obesity was more frequent in the former group (62.9% vs 35.4%, P<0.0001). Prevalence of hypertension (37% vs 27.5%, P=0.03), diabetes (14% vs 6.7%, P=0.01), and OSA (18.2% vs 10.4%, P=0.035) was also higher in individuals reporting sleepiness during the day. In multivariable analysis adjusted for age, sex, and OSA, daytime sleepiness was associated with increased risk of obesity (OR=2.88, 95% CI 1.84–4.49, P<0.0001), hypertension (OR=1.73, 95% CI 1.04–2.87, P=0.034), and diabetes (OR=2.58, 95% CI 1.18–5.61, P=0.017).ConclusionDaytime sleepiness is associated with greater risk of obesity, hypertension and diabetes independently of comorbid OSA. Daytime sleepiness may be a novel target for preventative and therapeutic strategies aimed at improving cardiometabolic health.Support or Funding InformationNC is supported by American Heart Association grant 16SDG27250156, and Mayo Clinic Center for Clinical and Translational Science grant Marie Ingalls Cardiovascular Research Career Development Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Association between Habitual Coffee Consumption and Indices of Body Fat

BackgroundDespite strenuous public health efforts, obesity rates continue to rise globally, and contribute importantly to increased cardiometabolic morbidity and mortality. Dietary habits play a key role in the development and progression of obesity, and are the target of choice in preventative and therapeutic programs. Although preclinical studies have shown that caffeine may exert anti‐adipogenic effects, in humans the implications of coffee consumption on risks of excess adiposity are unclear.ObjectiveThe objective of this study was to investigate the association between habitual coffee consumption and indices of total and regional body fat in healthy adults.MethodsSeventy‐eight subjects (46 males, mean age 27.3±6.1 years) who took part in research studies conducted at the Mayo Clinic Cardiovascular/Sleep Laboratory and underwent body composition assessment were selected. Absence of cardiovascular or metabolic diseases was ascertained by physical exam and review of medical charts. Height, weight, waist and hip circumference measures were collected for computation of body mass index (BMI, kg/m2) and waist‐to‐hip ratio (WHR). Measurements of total body fat percentage, upper body fat (kg), and lower body fat (kg) were obtained from dual‐energy X‐ray absorptiometry (DXA). Abdominal computed tomography (CT) was used to quantify subcutaneous adipose tissue (SAT, cm2) and visceral adipose tissue (VAT, cm2). Habitual coffee consumption (cups/day; range 0–3) was self‐reported and coded as a binary variable (yes/no).ResultsSixty percent of the subjects (n=47) reported habitual coffee consumption. Age and gender distribution were comparable between groups (P=0.52 and P=0.73, respectively). There was no significant difference between those who reported consuming coffee and those who did not in terms of BMI (23.6±2.7 kg/m2 vs 24±2.8 kg/m2, P=0.56) and WHR (0.85±0.08 vs 0.85±0.07, P=0.7). Likewise, body composition and fat distribution indices were similar between groups: total body fat percentage (coffee drinkers vs non‐coffee drinkers: 30.5±7.2% vs 28.6±7.8%, P=0.27), upper body fat mass (6.6±2.4 kg vs 6.6±3.1 kg, P=0.99), lower body fat mass (9.4±5.2 kg vs 8.4±4.1 kg, P=0.39), SAT (143.4±61.3 cm2 vs 135.9±63.7 cm2, P=0.6), and VAT (57.7±35.5 cm2 vs 70.3±44 cm2, P=0.22). Analysis stratified by gender did not reveal any differential effect of regular coffee consumption on body fat (all Ps>0.26).ConclusionIn healthy, young individuals moderate habitual coffee consumption is not associated with measures of total or regional adiposity. Whether the anti‐obesity effects of caffeine emerge only when it is consumed in larger quantities remains to be determined.Support or Funding InformationResearch support: NC is supported by American Heart Association grant 16SDG27250156 and Mayo Clinic Center for Clinical and Translational Science grant Marie Ingalls Cardiovascular Research Career Development Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Myocardial Slices: an Intermediate Complexity Platform for Translational Cardiovascular Research

Myocardial slices, also known as “cardiac tissue slices” or “organotypic heart slices,” are ultrathin (100–400 μm) slices of living adult ventricular myocardium prepared using a high-precision vibratome. They are a model of intermediate complexity as they retain the native multicellularity, architecture, and physiology of the heart, while their thinness ensures adequate oxygen and metabolic substrate diffusion in vitro. Myocardial slices can be produced from a variety of animal models and human biopsies, thus providing a representative human in vitro platform for translational cardiovascular research. In this review, we compare myocardial slices to other in vitro models and highlight some of the unique advantages provided by this platform. Additionally, we discuss the work performed in our laboratory to optimize myocardial slice preparation methodology, which resulted in highly viable myocardial slices from both large and small mammalian hearts with only 2–3% cardiomyocyte damage and preserved structure and function. Applications of myocardial slices span both basic and translational cardiovascular science. Our laboratory has utilized myocardial slices for the investigation of cardiac multicellularity, visualizing 3D collagen distribution and micro/macrovascular networks using tissue clearing protocols and investigating the effects of novel conductive biomaterials on cardiac physiology. Myocardial slices have been widely used for pharmacological testing. Finally, the current challenges and future directions for the technology are discussed.

A complete workflow for the differentiation and the dissociation of hiPSC-derived cardiospheres

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in downstream applications, either as monolayers or spheroids.

Meet the First Authors.

Meet the First Authors.

A Special Section on Novel Technologies and Scientific Advances in Translational Cardiovascular and Neurological Research

<i>A Special Section on</i> Novel Technologies and Scientific Advances in Translational Cardiovascular and Neurological Research