Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model

BACKGROUND AND OBJECTIVES@#We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model.@*METHODS@#Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment.@*RESULTS@#Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4uclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment.@*CONCLUSIONS@#These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model

BACKGROUND AND OBJECTIVES: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model.METHODS: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment.RESULTS: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment.CONCLUSIONS: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

Spontaneous Low-Frequency Cerebral Hemodynamics Oscillations in Restless Legs Syndrome with Periodic Limb Movements During Sleep: A Near-Infrared Spectroscopy Study

BACKGROUND AND PURPOSE: Periodic limb movements (PLM) during sleep (PLMS) are associated with cortical and cardiovascular activation. Changes in cerebral hemodynamics caused by cortical activity can be measured using near-infrared spectroscopy (NIRS). We investigated oscillatory components of cerebral hemodynamics during PLM and different sleep stages in restless legs syndrome (RLS) patients with PLMS. METHODS: Four female RLS patients with PLMS, and four age- and sex-matched normal controls were included. PLM and sleep stages were scored using polysomnography, while the spontaneous cerebral hemodynamics was measured by NIRS. The phase and amplitude of the cerebral oxyhemoglobin concentration [HbO] and the deoxyhemoglobin concentration [Hb] low-frequency oscillations (LFOs) were evaluated during each sleep stage [waking, light sleep (LS; stages N1 and N2), slow-wave sleep (stage N3), and rapid eye movement (REM) sleep]. In RLS patients with PLMS, the cerebral hemodynamics during LS was divided into LS with and without PLM. RESULTS: The cerebral hemodynamics activity varied among the different sleep stages. There were changes in phase differences between [HbO] and [Hb] LFOs during the different sleep stages in the normal controls but not in the RLS patients with PLMS. The [HbO] and [Hb] LFO amplitudes were higher in the patient group than in controls during both LS with PLM and REM sleep. CONCLUSIONS: The present study has demonstrated the presence of cerebral hemodynamics disturbances in RLS patients with PLMS, which may contribute to an increased risk of cerebrovascular events.

Development of Steroid Myopathy during Polymyositis Treatment / 영남의대학술지

Polymyositis is diffuse, inflammatory myopathy with proximal-muscle weakness due to lymphocyte infiltration to the muscle layer. The exact cause of the muscle weakness is unclear but may be related with an immunologic mechanism. Using high-dose steroid is the treatment of choice for polymyositis. It is difficult to distinguish steroid-resistant polymyositis from steroid myopathy, however, in the course of high-dose steroid therapy. These authors encountered a steroid myopathy patient during polymyositis treatment with high-dose steroid. A 57-year-old woman was diagnosed with polymyositis and was treated with high-dose steroid. Her condition was initially improved, but in the course of the treatment, her symptom was aggravated without increasing the muscle enzymes. Her muscle weakness was improved by reducing the steroid dosage.