scholarly journals Chloroquine differentially modulates coronary vasodilation in control and diabetic mice

2020 ◽  
Vol 177 (2) ◽  
pp. 314-327 ◽  
Author(s):  
Qian Zhang ◽  
Atsumi Tsuji‐Hosokawa ◽  
Conor Willson ◽  
Makiko Watanabe ◽  
Rui Si ◽  
...  
Keyword(s):  
Diabetic Mice ◽  
Coronary Vasodilation

Abstract 17248: The Role of microRNA-21 in Regulating the Coronary Microcirculation in Diabetes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Cody Juguilon ◽  
Zhiyuan Wang ◽  
James Gadd ◽  
Vahagn A Ohanyan ◽  
Anurag Jamaiyar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Quantitative Polymerase Chain Reaction ◽  
Contrast Echocardiography ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Diabetic Mice ◽  
Coronary Vasodilation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Genetic Profiling ◽  
Synthase Inhibitor

Introduction: Coronary microvascular dysfunction is prevalent among diabetics and intersects with deficits in endothelial-dependent vasodilation. These deficits occur early in the progression of the disease, but the mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelial-dependent mediator of vasodilation in the healthy coronary circulation, but the mediator switches to hydrogen peroxide (H 2 O 2 ) in coronary artery disease (CAD) patients. Diabetes is a risk factor for CAD, so we hypothesized that a similar switch would occur. Methods: Coronary arteries were isolated and endothelial-dependent vasodilation was assessed using myography. Quantitative polymerase chain reaction (qPCR) was performed for gene expression analysis and myocardial blood flow (MBF) was measured by contrast echocardiography. Results: Nitric oxide synthase inhibitor (L-NAME) inhibited vasodilation in wild type (WT) mice, but the H 2 O 2 scavenger (PEG-catalase) had no effect. In contrast, vasodilation in diabetic mice was blunted by PEG-catalase, but not L-NAME. This suggests that the mediator of coronary vasodilation switched from NO to H 2 O 2 in diabetes. Importantly, we found that microRNA-21 (miR-21) is upregulated in diabetes and the deficiency modulates the mediator switch from NO to H 2 O 2 in diabetic mice. Conclusions: The switch in the mediator of coronary vasodilation from NO to H2O2 contributes to microvascular dysfunction in diabetes and miR-21 regulates this switch. Further genetic profiling will elucidate the pathways and mechanisms converging with miR-21 to regulate microvascular function in diabetes. This is the first mouse model that recapitulates the switch in mediator of coronary vasodilation from NO to H 2 O 2 seen in CAD patients.

Anti-Diabetic Activity of a Mineraloid Isolate, in vitro and in Genetically Diabetic Mice

2011 ◽  
Vol 81 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Joel Deneau ◽  
Taufeeq Ahmed ◽  
Roger Blotsky ◽  
Krzysztof Bojanowski
Keyword(s):  
Dna Microarrays ◽  
Human Fibroblasts ◽  
Diabetic Animal ◽  
In Vitro Tests ◽  
Diabetic Mice ◽  
Fossil Material ◽  
Expression Of Genes ◽  
Enhanced Expression ◽  
Genetically Diabetic Mice

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.

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