Virginie Bito

Myocardial infarction (MI) causes extensive cardiomyocyte loss and adverse remodeling, frequently progressing to heart failure. Although stem cell-based therapies are being investigated for cardiac repair, clinical outcomes remain modest. Cardiac atrial appendage stem cells (CASCs) harbor cardiomyogenic potential, making them promising candidates for cardiac regeneration. This proof-of-concept pilot study investigates the feasibility and preliminary therapeutic potential of delivering CASCs within an elastin-like recombinamer (ELR) hydrogel scaffold following MI. MI was induced in rats by permanent ligation of the left anterior descending coronary artery. Immediately after occlusion, CASCs (MI+C), ELR hydrogel (MI+H), or CASCs embedded in ELR hydrogel (MI+C+H) were injected intramyocardially into the peri-infarct region. MI and SHAM-operated animals served as controls. Four weeks post-MI, echocardiography showed a large, non-significant left ventricular ejection fraction improvement in MI+C+H versus MI, with a trend toward reduced end-diastolic volume. MI+C+H significantly improved anterior wall thickness versus MI+H, with favorable trends for MI+C. Wall motion score index showed a similar large, non-significant effect. Transcriptomics suggested the MI+C+H molecular profile reflected complementary contributions of both monotherapies rather than distinct synergistic mechanisms. These preliminary findings support ELR-mediated CASC delivery and suggest potential benefits for preserving cardiac function and limiting adverse remodeling, warranting confirmation in adequately powered studies.

Initial ELP expression is streamlined by combining Design of Experiments with Western blot densitometry, creating a resource-efficient protocol that eliminates the need for upstream purification.

Cardiomyopathy is a major complication of type 2 diabetes, whose prevalence continues to rise globally. Although major cardiology and endocrinology societi

Hypertension is a leading contributor to cardiovascular morbidity and mortality. Trace elements such as cadmium (Cd), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) modulate blood pressure through oxidative stress, endothelial dysfunction, and metabolic regulation. Although previous studies have largely focused on individual elements, the combined effects of trace elements remain poorly understood. This systematic review summarizes observational evidence regarding associations between blood trace element concentrations and hypertension, and evaluate potential interactive effects among multiple trace elements. We systematically searched PubMed, Wiley, Google Scholar, and Web of Science for studies published between 1970 and 2025 reporting blood trace element concentrations in hypertensive and normotensive adults. Sixteen studies met the inclusion criteria. Pooled mean differences (MD) and standardized mean differences (SMD) were calculated using random-effects models. Heterogeneity, publication bias, and potential interactions among trace elements were assessed. A value p < 0.05 was considered statistically significant. Cd and Cu concentrations were higher in hypertensive individuals (Cd: MD = 4.67, 95% CI: 0.25–9.10; SMD = 2.48, 95% CI: 0.18–5.25; I² = 99.4%; Cu: MD = 19.18, 95% CI: 4.48–33.87; SMD = 0.86, 95% CI: 0.26–1.46; I² = 99.6%), although heterogeneity was extremely high. No consistent associations were observed for Zn, Fe, Mg, or Se. Very few studies assessed interactions between multiple trace elements. Evidence suggested no significant difference in the Zn/Cu ratio between hypertensive and normotensive groups.. Elevated blood concentrations of Cd and Cu are statistically associated with adult hypertension; however, these association should be considered hypothesis-generating, as evidence for other trace elements remains inconclusive. The limited research on co-exposures highlights the need for future studies employing multivariate and interaction models to better understand the role of trace element interactions in hypertension.

Rodents models of myocardial infarction (MI) continue to be frequently used in preclinical cardiovascular research, despite alternative approaches being on the rise. The commonly used coronary artery permanent ligation (PL) approach is often hampered by substantial perioperative mortality and variable success rates. We optimized the rat PL protocol by relying exclusively on isoflurane inhalation anesthesia by introducing a standardized intubation setup, maintaining strict control of body temperature throughout surgery, and surgical technique refinements. The latter included gentle mobilization of the Pectoralis major and thymus, a medial thoracotomy through the third intercostal space, and the use of a reference ligature to facilitate reliable identification and ligation of the left anterior descending coronary artery (LAD). Cardiac rhythm was continuously monitored, and extubation was carefully timed to reduce complications. With this protocol, perioperative mortality was reduced to zero and successful ligation was obtained in 94% of animals (n = 172). Echocardiography and histology confirmed consistent induction of infarcts. By lowering invasiveness and improving survival and reproducibility, the refined PL method enhances both the reliability of preclinical research and compliance with the 3Rs, representing a meaningful step forward for studies in cardiac regeneration.

Echocardiography-guided intramyocardial injection (EGI) is a minimally invasive technique for delivering stem cell therapies in preclinical myocardial infarction (MI) models. Compared to traditional open-chest approaches, EGI offers improved clinical translatability, reduced invasiveness, and minimized physiological impact on the animal. While EGI is well established in murine models, its application in rats remains limited due to anatomical and technical challenges. In particular, thinning of the left ventricular anterior wall (LVAW) in infarcted and peri-infarct regions complicates safe and accurate myocardial delivery, as wall thickness can fall below the needle bevel size of commonly used 27 G or 28 G needles, increasing the risk of ventricular perforation or failed delivery. To address this limitation, we optimized a protocol for EGI in rat MI models using 29 G Spinocan needles. The smaller-diameter, longer needle enables precise targeting of thin myocardial tissue, minimizing damage and enhancing injection accuracy, independent of LVAW thickness. This technique is compatible with standard transthoracic echocardiography platforms and eliminates the need for thoracotomy, allowing longitudinal studies in the same animal. Our refined method enables robust, reproducible delivery of therapeutic agents into viable myocardium adjacent to the infarct zone, where regenerative therapies are most effective. By improving safety and targeting precision, this approach increases the translational relevance of preclinical cardiac research and supports the development of standardized protocols across laboratories.

Echocardiography-guided intramyocardial injection (EGI) is a minimally invasive technique for delivering stem cell therapies in preclinical myocardial infarction (MI) models. Compared to traditional open-chest approaches, EGI offers improved clinical translatability, reduced invasiveness, and minimized physiological impact on the animal. While EGI is well established in murine models, its application in rats remains limited due to anatomical and technical challenges. In particular, thinning of the left ventricular anterior wall (LVAW) in infarcted and peri-infarct regions complicates safe and accurate myocardial delivery, as wall thickness can fall below the needle bevel size of commonly used 27 G or 28 G needles, increasing the risk of ventricular perforation or failed delivery. To address this limitation, we optimized a protocol for EGI in rat MI models using 29 G Spinocan needles. The smaller-diameter, longer needle enables precise targeting of thin myocardial tissue, minimizing damage and enhancing injection accuracy, independent of LVAW thickness. This technique is compatible with standard transthoracic echocardiography platforms and eliminates the need for thoracotomy, allowing longitudinal studies in the same animal. Our refined method enables robust, reproducible delivery of therapeutic agents into viable myocardium adjacent to the infarct zone, where regenerative therapies are most effective. By improving safety and targeting precision, this approach increases the translational relevance of preclinical cardiac research and supports the development of standardized protocols across laboratories.

Aims: Anthracycline-induced cardiotoxicity has high incidence rates and causes significant mortality among cancer survivors. Damage to myocardial tissue leads to left ventricular (LV) dilation with systolic dysfunction, typically assessed through echocardiographic measurement of LV ejection fraction (LVEF) and volumes. Early detection is crucial for improving patient outcomes. We aimed to evaluate cardiotoxicity progression and diagnostic performance of different echocardiographic modalities in an animal model. Methods and results: Female Sprague Dawley rats received either intravenous doxorubicin (DOX) injections weekly for 8 weeks (2 mg/kg/week) or saline (control). Transthoracic LV echocardiography was performed before treatment and at 4, 6, and 8 weeks in the treatment course. Two researchers performed and evaluated M-mode, B-mode, and four-dimensional (4D) echocardiography. Bland–Altman plots were created to show the bias and limits of agreement when comparing echocardiographic modalities. Simple linear regression and Pearson correlation were applied to evaluate interobserver variability. Six weeks after the first DOX injection, LVEF, radial LV fractional shortening, LV end-systolic volume, and LV end-diastolic volume were significantly reduced compared with baseline. LV dysfunction and dilation became more pronounced after 8 weeks of DOX treatment. For all parameters, 4D- and M-mode showed the lowest bias and narrowest limits of agreement. The correlation between the researchers’ measurements was strong for most parameters. Conclusion: Our rat model of DOX-induced cardiotoxicity demonstrates that volumetric changes are more pronounced. Both 4D- and M-mode imaging techniques proved effective and reliable compared with the standard B-mode approach, with minimal interobserver variability, indicating strong reproducibility.

Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk for heart failure, yet preventive cardiac care is suboptimal in this population. Pyridoxamine (PM), a vitamin B₆ analog, has been shown to exert protective effects in metabolic and cardiovascular diseases. In this study, we aimed to investigate whether PM limits adverse cardiac remodeling and dysfunction in rats who develop T2DM. Male rats received a standard chow diet or Western diet (WD) for 18 weeks to induce prediabetes. One WD group received additional PM (1 g/L) via drinking water. Glucose tolerance was assessed with a 1 h oral glucose tolerance test. Cardiac function was evaluated using echocardiography and hemodynamic measurements. Histology on left ventricular (LV) tissue was performed. Treatment with PM prevented the increase in fasting plasma glucose levels compared to WD-fed rats (p < 0.05). LV cardiac dilation tended to be prevented using PM supplementation. In LV tissue, PM limited an increase in interstitial collagen deposition (p < 0.05) seen in WD-fed rats. PM tended to decrease 3-nitrotyrosine and significantly lowered 4-hydroxynonenal content compared to WD-fed rats. We conclude that PM alleviates interstitial fibrosis and oxidative stress in the hearts of WD-induced prediabetic rats.

Microglia activity can drive excessive synaptic loss during the prodromal phase of Alzheimer’s disease (AD) and is associated with lowered cyclic adenosine monophosphate (cAMP) due to cAMP phosphodiesterase 4B (PDE4B). This study aimed to investigate whether long-term inhibition of PDE4B by A33 (3 mg/kg/day) can prevent synapse loss and its associated cognitive decline in APPswe/PS1dE9 mice. This model is characterized by a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9 (dE9), both under the control of the mouse prion protein promoter. The effects on cognitive function of prolonged A33 treatment from 20 days to 4 months of age, was assessed at 7–8 months. PDE4B inhibition significantly improved both the working and spatial memory of APPswe/PSdE9 mice after treatment ended. At the cellular level, in vitro inhibition of PDE4B induced microglial filopodia formation, suggesting that regulation of PDE4B activity can counteract microglia activation. Further research is needed to investigate if this could prevent microglia from adopting their ‘disease-associated microglia (DAM)’ phenotype in vivo. These findings support the possibility that PDE4B is a potential target in combating AD pathology and that early intervention using A33 may be a promising treatment strategy for AD.