Views
3 months ago

2017 Cardiovascular Research Day Abstract Book

75 Inducible Depletion

75 Inducible Depletion of Calpain-2 Attenuates Obesity-accelerated Abdominal Aortic Aneurysms in mice Aida Javidan, MS 1 • Weihua Jiang, MS 1 • Jessica Moorleghen, MS 1 • Venkateswaran Subramanian, PhD 2 1Saha Cardiovascular Research Center, University of Kentucky • 2 Physiology, University of Kentucky Graduate Student Background and Objective: Recent clinical studies demonstrated that abdominal adiposity is associated with increased risk of abdominal aortic aneurysm (AAA) development. Calpains are nonlysosomal calcium dependent cysteine proteases that are highly expressed in human and experimental AAAs. Using a pharmacological inhibitor and genetically deficient mice, we identified that calpain-2 (a major ubiquitous isoform) plays a critical role in Angiotensin II (AngII)-induced AAA formation in mice. In addition, calpain inhibition strongly suppressed adipose tissue inflammation in obese mice. The purpose of this study was to determine the functional contribution of calpain-2 in obesity-accelerated AAA. Methods and Results: Calpain-2 floxed mice that were hemizygous for β-actin Cre-ERT2 were produced by breeding male Cre-ERT2 to female calpain-2 floxed mice. At 8 weeks of age, male non- Cre littermates (Cre-) and Calp-2 x Cre-ERT2 (Cre+) mice were injected with tamoxifen (25 mg/kg, i.p.) daily for 5 consecutive days. After 2 weeks, Western blot analyses showed a complete depletion of calpain-2 protein in the aorta and periaortic adipose tissue from Cre+ mice compared to non-Cre littermates. Mice were fed a high fat diet (60% Kcal) for 20 weeks. After 16 weeks of diet feeding, mice were infused with AngII (1,000 ng/kg/min) by osmotic minipumps for 4 weeks. Depletion of calpain-2 had no effect on high fat diet-induced body weight gain, fat mass, glucose and insulin tolerance. Interestingly, calpain-2 depletion significantly attenuated AngII-induced expansion of exvivo maximal diameter of abdominal aortas in obese mice (Cre-: 1.4 ± 0.14; Cre+: 0.9 ± 0.04 mm; P

76 Pancreatic Beta Cell Export of miR-375 to High-Density Lipoproteins is Regulated by Cellular Ion Fluxes. Leslie Sedgeman 1 • Carine Beysen, PhD 2 • Marisol Ramirez-Solano 3 • Quanhu Sheng, PhD 4 • Yan Guo, PhD 4 • Scott Turner, PhD 2 • Kasey Vickers, PhD 3 1Molecular Physiology and Biophysics, Vanderbilt University • 2 Kinemed, Inc. • 3 Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center • 4Department of Cancer Biology, Vanderbilt University Medical Center Graduate Student microRNAs (miRNAs) are critical regulators of glucose metabolism and contribute to the pathogenesis of Type 2 Diabetes (T2D). Recently, we reported that high-density lipoproteins (HDL) transport and deliver functional miRNAs to recipient cells, including endothelial cells and hepatocytes. However, the mechanism of export is not understood. Since miR-375 expression in the islets is 10X greater than in other organs, we tested whether pancreatic beta cells have the ability to export miR-375 to HDL through in vitro export assays, incubating HDL with INS1 beta cells or primary human islets. Indeed, we found miR-375 to be readily exported to HDL from INS1 cells and primary islets in vitro. To determine if cholesterol transporters contribute to HDL-miR-375 export from beta cells, Abca1, Abcg1 and Scarb1 (SR-BI) were inhibited using siRNAs; however, we found that knockdown of each of these transporters failed to affect the beta cell’s ability to export miR- 375 to HDL. On the other hand, inhibition of the KATP channel with tolbutamide resulted in the suppression of HDL-miR-375 export. Similarly, export of miR-375 to HDL was blunted from islets of two mouse models lacking functional KATP channels (Kir6.2 and SUR1 KO mice). Our work suggests that miR-375 export to HDL is regulated by cellular dynamics, including ion fluzes in the beta cell. We are currently investigating the relationship between HDL-miR-375 export, insulin secretion, and miRNA processing in pancreatic beta cells to further elucidate the mechanism(s) controlling HDL-miR-375 export. Collectively, results suggest that a large fraction of HDL-miRNAs originate from pancreatic beta cells and HDL-miRNAs are exported independent of cholesterol transporters. 92

Abstract Book Research Day 2013.pdf - University of Minnesota ...
Research Day Book 2013 - College of Medicine - Florida Atlantic ...
Assessment of Tobacco Smoke-Mediated Atherosclerosis in Mouse ...
Book of Abstracts - Australian Centre for Economic Research on ...
Research Days 2013 Abstract Book - Office of the Vice President for ...
2010 Abstracts - Radiation Research Society
Abstract Booklet - University of Ottawa Heart Institute
Abstract Book - Pathology and Laboratory Medicine - University of ...
book of abstracts 11th annual research half day may 12, 2010 ...
research day - University of Toronto Department of Obstetrics and ...
Abstracts - Society of Cardiovascular Anesthesiologists
Abstracts - Interactive CardioVascular and Thoracic Surgery
Abstracts for The European Society for Cardiovascular Surgery 53rd ...
CARDIOVASCULAR DISEASE IN WOMEN - Epib.nl
PATHOLOGY OF THE CARDIOVASCULAR SYSTEM Dr: Khitam Dr ...
Conditional Risk Factors for Atherosclerosis - Mayo Medical ...
Oral Presentations - Arteriosclerosis, Thrombosis, and Vascular ...
Reverse cholesterol transport and cholesterol efflux in atherosclerosis
Technologist Abstracts - Society of Cardiovascular Magnetic ...
The interplay of inflammation and cardiovascular disease in ...
Book of Abstracts - Oxygen Club of California
Book of Abstracts - Oxygen Club of California
Cardiovascular Lab Indicators - Anaturalhealingcenter.com
Research Days Abstract Book - Office of the Vice President for ...