scholarly journals MicroRNA-133a impairs perfusion recovery after hindlimb ischemia in diabetic mice

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Lingdan Chen ◽  
Chunli Liu ◽  
Dejun Sun ◽  
Tao Wang ◽  
Li Zhao ◽  
...  

Objective: Peripheral arterial disease (PAD) patients with diabetes mellitus suffer from impaired neovascularization after ischemia which results in poorer outcomes. MicroRNA (miR)-133a is excessively expressed in endothelial cells under diabetic conditions. Here, we test whether diabetes-induced miR-133a up-regulation is involved in the impaired capability of neovascularization in experimental PAD models. Methods and results: MiR-133a level was measured by quantitative RT-PCR and showed a higher expression level in the ischemic muscle from diabetic mice when compared with nondiabetic mice. Knockdown of miR-133a using antagomir improved perfusion recovery and angiogenesis in experimental PAD model with diabetes day 21 after HLI. On the other hand, overexpression of miR-133a impaired perfusion recovery. Ischemic muscle was harvested day 7 after experimental PAD for biochemical test, miR-133a antagonism resulted in reduced malondialdehyde, and it increased GTP cyclohydrolase 1 (GCH1), and cyclic guanine monophosphate (cGMP) levels. In cultured endothelial cells, miR-133a antagonism resulted in reduced reactive oxygen species level, and it increased tube formation, nitric oxide (NO), and cGMP level. Moreover, miR-133a antagonism-induced angiogenesis was abolished by GCH1 inhibitor. In contrary, miR-133a overexpression impairs angiogenesis and it reduces GCH1, NO, and cGMP levels in nondiabetic models. Conclusion: Diabetes mellitus-induced miR-133a up-regulation impairs angiogenesis in PAD by reducing NO synthesis in endothelial cells. MiR-133a antagonism improves postischemic angiogenesis.

2016 ◽  
Vol 15 (1) ◽  
pp. 42-49 ◽  
Author(s):  
D. A. Usanov ◽  
A. V. Skripal ◽  
S. N. Potakhin ◽  
A. A. Sagaidachnyi ◽  
A. V. Fomin ◽  
...  

The aim of the study - thermography-based analysis of lower limb vascular response to thermal impact in patients with trophic disorders, diabetes mellitus and peripheral atherosclerosis. Materials and methods. Thermal impact was carried out using the heating pad acting for 20 minutes. Control of temperature of back of the feet was performed by thermal imaging camera with a thermal sensitivity of 0.02°C. The study involved a group of 8 subjects without vascular disorders of the lower limbs (controls), and patient group of 8 subjects with trophic disorders due to the progression of diabetes and atherosclerosis (age of 67±8 years). All patients had type 2 diabetes and peripheral arterial disease with different levels and the degree of the main arterial occlusion. Intensity of trophic disorders changed from apical necrosis and trophic ulcers to gangrene of the foot. We calculated spectral amplitude parameters and temperature dynamics. Fourier transform was used to perform spectral analysis of temperature data. Results. Temperature response of limbs in patients with diabetes compared with healthy subjects was characterized by monotonous temperature variation without distinct oscillations; reduction in amplitude of oscillations within endothelial temperature range; relatively high average temperature difference between the left and right foot. In the group of healthy subjects reaction on thermal impact is not strictly two-stage, usually interpretable by theory as primary and secondary vasodilation. Conclusions. Decrease of temperature amplitude of endothelial range registered during thermal impact can be the sign of endothelial dysfunction in patients with diabetes and peripheral arterial disease. Spectral and temperature characteristics of reaction of limbs on thermal impact can be used to assess trophic disorders and compensation mechanisms of regulation of metabolic processes in the group of patients with diabetes mellitus.


2013 ◽  
Vol 03 (02) ◽  
pp. 79-85 ◽  
Author(s):  
Javier Ena ◽  
Carlos R. Argente ◽  
Víctor González-Sánchez ◽  
Natividad Algado ◽  
Gema Verdú ◽  
...  

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