Abstract: SA-PO314
The Effect of the Sodium-Glucose Co-Transporter-2 Inhibitor in Angiogenesis of Diabetic Cardiovascular Disease
Session Information
- Hypertension and CVD: Mechanisms
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1402 Hypertension and CVD: Clinical, Outcomes, and Trials
Authors
- Chan, Jenq-shyong, Division of Nephrology,Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taiwan, Taoyuan, Taiwan
- Roy-Chaudhury, Prabir, University of North Carolina, Chapel Hill, North Carolina, United States
- Wu, Tao-cheng, Division of Cardiology, Department of Internal Medicine,Taipei Veterans General Hospital, Taipei, Taiwan
Background
Diabetic patients with peripheral arterial occlusive disease (PAOD) are at high risk from cardiovascular events, vascular death and ischemic ulceration .The most importantl induction of collateral vessels is essential to the initiation of angiogenesis.
A sodium–glucose co-transporter-2 (SGLT-2) inhibitor (Dapagliflozin), is a novel class of antihyperglycaemic agent.In present study, we can evaluate the effects of SGLT2 inhibitors in diabetic mice with PAOD by cell and animal studies.
Methods
Chronic hind-limb ischaemia (15 mice) by ligating and transecting the left common femoral artery.
Laser Doppler measurement of tissue blood flow to detect hind-limb blood flows
Human Endothelial progenitor cell culture were cultured in 5% CO2 at 370C in cell growth medium. Cells from passages 4–8 were used for all experiments.
MTT assay
Cells were treated with variable concentration of dapagliflozin for 24 hours with hydrogen peroxide, washed with phosphate buffered solution, incubated in a conditioned medium for 1 hour with 2 μg/mL MTT, and then were lysed. Absorbance was measured at 570 nm using a spectrophotometric microplate reader (Multiskan EX, Labsystems; Helsinki, Finland).
EPC migration assay was evaluated by a modified Boyden chamber assay.The magnitude of migration of late EPCs was evaluated by counting the migrated cells in six random high-power fields.
EPC tube formation assay was performed with an In Vitro Angiogenesis Assay Kit(Chemicon). The average of the total area of complete tubes formed by cells was compared by using computer software, Image-Pro Plus.
Results
Dapagliflozin enhanced flow recovery in diabetic mice. Treatment of EPCs with dapagliflozin significantly increased tube formation and up-regulated impaired eNOS production and Akt action in hyperglycemic
Conclusion
SGLT-2 inhibitor improves blood flow recovery in diabetic mice with hind limb ischemia and promotes the functions of EPCs via NO-related pathways.
Funding
- Government Support - Non-U.S.