Objective To determine the plasma urolensin Ⅱ(UⅡ) levels in various types of coronary heart disease and to clarify how the plasma UⅡ levels correlate with the clinical presentation, extent and severity of coronary artery atherosclerosis (CAD). Methods: One hundred and three aged patients undergoing elective diagnostic coronary angiography for proven or clinical suspected coronary heart disease were enrolled in this study. The extent and severity of coronary artery disease were evaluated by vessel score and Gensini score, respectively. Plasma UⅡ levels were measured by radioimmunoassay. Results: The plasma UⅡ levels in the patients with modest to severe coronary stenosis (3.03±0.34 pg/ml, 1.83±0.67 pg/ml) were significantly lower than that in subjects with normal coronary artery (4.80±1.11 pg/ml, P＜0.001). The plasma UⅡ levels in patients with coronary heart disease were also significantly lower than that in patients with insignificant coronary stenosis (P ＜ 0.001). Compared to patients with stable angina pectoris, plasma UⅡ levels in patients with acute coronary syndrome were significantly decreased (1.89±0.51 pg/ml vs 2.42±0.77 pg/ml, P＜ 0.001). Plasma UⅡ levels were found to be negatively correlated with the severity of coronary artery stenosis (r = -0.488, P＜0.001), as well as the vessel score (r = -0.408, P＜0.05) in the patients with CAD. Conclusion: Significant inverse correlations exist between the plasma UⅡ levels, and the extent and severity of coronary artery stenosis. These findings suggest that plasma UⅡ contribute to the development and progression of coronary artery stenosis, and may be a novel marker to predict clinical types, as well as the extent and severity of coronary artery disease in the patients.

To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment. We reviewed the pharmacological agents which reduced the risk of HT associated with delayed (beyond 4.5 hours post-stroke) tPA treatment in preclinical studies, which we classified into those that putatively preserve the blood-brain barrier (e.g., minocycline, cilostazol, fasudil, candesartan, and bryostatin) and/or enhance vascularization and protect the cerebrovasculature (e.g., coumarin derivate IMM-H004 and granulocyte colony-stimulating factor). Recently, other new therapeutic modalities (e.g., oxygen transporters) have been reported which improved delayed tPA-associated outcomes by acting through other mechanisms. While the above-mentioned interventions unequivocally reduced delayed tPA-induced HT in stroke models, the long-term efficacy of these drugs are not yet established. Further optimization is required to expedite their future clinical application. The findings from this review indicate the need to explore the most ideal adjunctive interventions that will not only reduce delayed tPA–induced HT, but also preserve neurovascular functions. While waiting for the next breakthrough drug in acute stroke treatment, it is equally important to allocate considerable effort to find approaches to address the limitations of the only FDA-approved stroke therapy.
Blood-Brain Barrier ; Granulocytes ; Hand ; Hemorrhage ; Humans ; Minocycline ; Mortality ; Oxygen ; Reperfusion ; Stroke* ; Tissue Plasminogen Activator