Jung-Tung Liu

Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization.

Epigallocatechin gallate attenuates proliferation and oxidative stress in human vascular smooth muscle cells induced by interleukin-1β via heme oxygenase-1.

Proliferation of vascular smooth muscle cells (VSMCs) triggered by inflammatory stimuli and oxidative stress contributes importantly to atherogenesis. The association of green tea consumption with cardiovascular protection has been well documented in epidemiological observations, however, the underlying mechanisms remain unclear. This study aimed to elucidate the effects of the most active green tea catechin derivative, (−)-epigallocatechin-3-gallate (EGCG), in human aortic smooth muscle cells (HASMCs), focusing particularly on the role of a potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1). We found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein levels in HASMCs. EGCG inhibited interleukin- (IL-)1β-induced HASMC proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer CoPPIX decreased IL-1β-induced cell proliferation, whereas the HO-1 enzyme inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1β-treated HASMCs. At the molecular level, EGCG treatment significantly activated nuclear factor erythroid-2-related factor (Nrf2) transcription activities. These results suggest that EGCG might serve as a complementary and alternative medicine in the treatment of these pathologies by inducing HO-1 expression and subsequently decreasing VSMC proliferation.

Red Yeast Rice Protects Circulating Bone Marrow-Derived Proangiogenic Cells against High-Glucose-Induced Senescence and Oxidative Stress: The Role of Heme Oxygenase-1

The inflammation and oxidative stress of bone marrow-derived proangiogenic cells (PACs), also named endothelial progenitor cells, triggered by hyperglycemia contributes significantly to vascular dysfunction. There is supporting evidence that the consumption of red yeast rice (RYR; Monascus purpureus-fermented rice) reduces the vascular complications of diabetes; however, the underlying mechanism remains unclear. This study aimed to elucidate the effects of RYR extract in PACs, focusing particularly on the role of a potent antioxidative enzyme, heme oxygenase-1 (HO-1). We found that treatment with RYR extract induced nuclear factor erythroid-2-related factor nuclear translocation and HO-1 mRNA and protein levels in PACs. RYR extract inhibited high-glucose-induced (30 mM) PAC senescence and the development of reactive oxygen species (ROS) in a dose-dependent manner. The HO-1 inducer cobalt protoporphyrin IX also decreased high-glucose-induced cell senescence and oxidative stress, whereas the HO-1 enzyme inhibitor zinc protoporphyrin IX and HO-1 small interfering RNA significantly reversed RYR extract-caused inhibition of senescence and reduction of oxidative stress in high-glucose-treated PACs. These results suggest that RYR extract serves as alternative and complementary medicine in the treatment of these diseases, by inducing HO-1, thereby decreasing the vascular complications of diabetes.

Insights Into Microcirculation Underlying Critical Limb Ischemia by Single-Photon Emission Computed Tomography.

AbstractPerfusion difference is used as a parameter to evaluate microcirculation. This study aims to differentiate lower-limb perfusion insufficiency from neuropathy to prevent possible occurrence of failed back surgery syndrome (FBSS).Patients were retrospectively gathered from 134 FBSS cases diagnosed in the past 7 years. Up to 82 cases that were excluded from neuralgia by radiologic imaging, electrodiagnostic electromyography, and nerve conduction velocity were enrolled in this study. Perfusion difference was evaluated by single-photon emission computed tomography, and pain intensities were recorded via visual analog scale (VAS) score.Lower perfusion at the left leg comprises 51.2% (42 of 82) of the patients. The mean perfusion difference of the 82 patients was 0.86 ± 0.05 (range: 0.75–0.93). Patients with systemic vascular diseases exhibited significantly higher perfusion difference than that of patients without these related diseases (P < 0.05), except for renal insufficiency (P = 0.134). Significant correlation was observed between perfusion difference and VAS score (r = −0.78; P < 0.0001; n = 82).In this study, we presented perfusion difference as a parameter for evaluating microcirculation, which cannot be detected by ultrasonography or angiography.

Brainstem Hemorrhage Caused by Direct Carotid-Cavernous Fistula: A Case Report and Literature Review

A 34-year-old woman presented with a history of persisting headache for years, and a newly developed dizziness, left facial palsy and right hemiparesis two days prior to this admission. Initial computed tomographic angiography of the head demonstrated an area of increased density in the left middle and posterior fossae. Multiple aneurysmally dilated venous ectasias with contrast enhancement at the left pre-pontine cistern causing a massive mass effect to the brainstem were also noted, suggesting a huge vascular abnormality. Digital subtraction angiography revealed an abnormal vascular lesion surrounding the brainstem, which indicated a left direct carotid-cavernous fistula with posterior drainage. As her consciousness deteriorated the next day, a follow-up computed tomography scan was done which revealed a pontine hemorrhage. Subsequently, endovascular closure of the fistula with sacrifice of the left ICA was performed, which successfully eliminated the imaging abnormalities.