echocardiography-guided-injection-for-targeted-reliable

Echocardiography-guided Injection for Targeted and Reliable Intramyocardial Stem Cell Delivery in a Rat Model of Myocardial Infarction

Echocardiography-guided intramyocardial injection (EGI) is a minimally invasive technique for delivering stem cell therapies in preclinical myocardial ...

Uhasselt

During myocardial infarction (MI), billions of cardiomyocytes are lost. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. As such, cardiac atrial appendage stem cells (CASCs) are suitable candidates. However, the presence of elevated levels of advanced glycation end products (AGEs) in cardiac regions where CASCs are transplanted may affect their regenerative potential. In this study, we examine whether and how AGEs alter CASCs properties in vitro.

Advanced Glycation End Products Impair Cardiac Atrial Appendage Stem Cells Properties.

Doxorubicin (DOX) is commonly used in cancer treatment but associated with cardiotoxicity. Pyridoxamine (PM), a vitamin B6 derivative, could be a cardioprotectant. This study investigated the effect of PM on DOX cardiotoxicity and DOX antitumor effectiveness. Sprague Dawley rats were treated intravenously with DOX (2 mg/kg/week) or saline over eight weeks. Two other groups received PM via oral intake (1 g/L in water bottles) next to DOX or saline. Echocardiography was performed after eight weeks. PM treatment significantly attenuated the DOX-induced reduction in left ventricular ejection fraction (72 ± 2% vs. 58 ± 3% in DOX;  < 0.001) and increase in left ventricular end-systolic volume (0.24 ± 0.02 µL/cm vs. 0.38 ± 0.03 µL/cm in DOX;  < 0.0001). Additionally, LA7 tumor cells were exposed to DOX, PM, or DOX and PM for 24 h, 48 h, and 72 h. Cell viability, proliferation, cytotoxicity, and apoptosis were assessed. DOX significantly reduced LA7 cell viability and proliferation ( < 0.0001) and increased cytotoxicity ( < 0.05) and cleaved caspase-3 ( < 0.001). Concomitant PM treatment did not alter the DOX effect on LA7 cells. In conclusion, PM attenuated DOX-induced cardiomyopathy in vivo without affecting the antitumor effect of DOX in vitro, highlighting PM as a promising cardioprotectant for DOX-induced cardiotoxicity.

Pyridoxamine Attenuates Doxorubicin-Induced Cardiomyopathy without Affecting Its Antitumor Effect on Rat Mammary Tumor Cells.

Endurance exercise training is a promising cardioprotective strategy in type 2 diabetes mellitus (T2DM), but the impact of its intensity is not clear. We aimed to investigate whether and how isocaloric moderate-intensity exercise training (MIT) and high-intensity interval exercise training (HIIT) could prevent the adverse cardiac remodeling and dysfunction that develop T2DM in rats. Male rats received a Western diet (WD) to induce T2DM and underwent a sedentary lifestyle ( = 7), MIT ( = 7) or HIIT ( = 8). Insulin resistance was defined as the HOMA-IR value. Cardiac function was assessed with left ventricular (LV) echocardiography and invasive hemodynamics. A qPCR and histology of LV tissue unraveled underlying mechanisms. We found that MIT and HIIT halted T2DM development compared to in sedentary WD rats ( < 0.05). Both interventions prevented increases in LV end-systolic pressure, wall thickness and interstitial collagen content ( < 0.05). In LV tissue, HIIT tended to upregulate the gene expression of an ROS-generating enzyme (NOX4), while both modalities increased proinflammatory macrophage markers and cytokines (CD86, TNF-α, IL-1β;  < 0.05). HIIT promoted antioxidant and dicarbonyl defense systems (SOD2, glyoxalase 1;  < 0.05) whereas MIT elevated anti-inflammatory macrophage marker expression (CD206, CD163;  < 0.01). We conclude that both MIT and HIIT limit WD-induced T2DM with diastolic dysfunction and pathological LV hypertrophy, possibly using different adaptive mechanisms.

Moderate-Intensity and High-Intensity Interval Exercise Training Offer Equal Cardioprotection, with Different Mechanisms, during the Development of Type 2 Diabetes in Rats.

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 B 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 ( < 0.05). LV cardiac dilation tended to be prevented using PM supplementation. In LV tissue, PM limited an increase in interstitial collagen deposition ( < 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.

Article	Year
Advanced Glycation End Products Impair Cardiac Atrial Appendage Stem Cells Properties. Journal of clinical medicine\| PubMed ID: 34279448	2021
Pyridoxamine Attenuates Doxorubicin-Induced Cardiomyopathy without Affecting Its Antitumor Effect on Rat Mammary Tumor Cells. Cells\| PubMed ID: 38247812	2024
Moderate-Intensity and High-Intensity Interval Exercise Training Offer Equal Cardioprotection, with Different Mechanisms, during the Development of Type 2 Diabetes in Rats. Nutrients\| PubMed ID: 38337716	2024
Pyridoxamine Alleviates Cardiac Fibrosis and Oxidative Stress in Western Diet-Induced Prediabetic Rats. International journal of molecular sciences\| PubMed ID: 39126079	2024

Ellen Heeren

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