Sodium Tanshinone IIA sulfonate improves post-ischemic angiogenesis in hyperglycemia.

Abstract

BACKGROUND:

Diabetes is a strong risk factor of peripheral arterial disease (PAD), and also leads to impaired perfusion recovery in the ischemic limb, which eventually results in poor outcomes in PAD patients. Sodium Tanshinone IIA Sulfonate (STS), a monomer from herbs, has been shown to improve the outcomes in a variety of ischemic disease including myocardial infarction. However, the effects of STS treatment in PAD is not known.

METHODS AND RESULTS:

Unilateral femoral artery was ligated in mice as experimental PAD models, STS treatment improved perfusion recovery, increased capillary densities, decreased reactive oxygen species (ROS) level and microRNA-133a (miR-133a) expression in the ischemic hindlimb in diabetic mice; however, STS did not change perfusion recovery in non-diabetic C57BL/6 mice. Ischemic muscle tissue from diabetic mice was harvested 7 days after femoral ligation for biochemical test, STS resulted in reduced malondialdehyde (MDA), and increased GTP cyclohydrolase 1 (GCH1) and cyclic guanine monophosphate (cGMP) levels. In addition, STS treatment increased miR-133a expression in endothelial cells isolated from ischemic muscle tissue of diabetic mice. In endothelial cells cultured in high glucose medium, STS increased tube formation and nitric oxide (NO) production, and reduced cellular ROS level and miR-133a expression under simulated ischemic condition. In addition, GCH1 inhibitor or miR-133a overexpression using exogenous microRNA mimic blunted STS-induced angiogenic effects and ROS neutralization in cultured endothelial cells under hyperglycemic and hypoxic conditions.

CONCLUSION:

These findings demonstrate STS improves angiogenesis via inhibiting miR-133a expression and increasing GCH-1 protein levels in experimental PAD with diabetes.

• Authors: Lingdan Chen, Wenjun He, Bin Peng, Mingjie Yuan, Neng Wang, Jian Wang, Wenju Lu, Tao Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 520 Issue 3 Pg. 580-585 (12 10 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31623833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• MicroRNAs
• Mirn133 microRNA, mouse
• Phenanthrenes
• Reactive Oxygen Species
• tanshinone II A sodium sulfonate

Topics

• Animals
• Diabetes Mellitus, Experimental (complications)
• Disease Models, Animal
• Drugs, Chinese Herbal (therapeutic use)
• Hindlimb (blood supply)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hyperglycemia (complications)
• Ischemia (drug therapy, etiology)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics, metabolism)
• Neovascularization, Physiologic (drug effects)
• Peripheral Arterial Disease (drug therapy, etiology)
• Phenanthrenes (therapeutic use)
• Phytotherapy
• Reactive Oxygen Species (metabolism)
• Salvia miltiorrhiza