ABSTRACT
BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
Subject(s)
Disease Models, Animal , Inflammasomes , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Mice, Inbred C57BL , Mice, Knockout, ApoE , NLR Family, Pyrin Domain-Containing 3 Protein , Phenanthrenes , Signal Transduction , Syk Kinase , Vasodilation , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Syk Kinase/metabolism , Matrix Metalloproteinase 2/metabolism , Phenanthrenes/pharmacology , Male , Matrix Metalloproteinase 9/metabolism , Vasodilation/drug effects , Hyperlipidemias/drug therapy , Hyperlipidemias/physiopathology , Vasodilator Agents/pharmacology , Phosphorylation , Mice , Aorta/drug effects , Aorta/physiopathology , Aorta/metabolism , Aorta/enzymology , Apolipoproteins EABSTRACT
Light relief! Mesoporous silica materials equipped with photoresponsive cucurbit[7]uril-pseudorotaxane nanovalves operate in biological media to trap cargo molecules within nanopores, but undergo controlled release when irradiated with light of a suitable wavelength (see figure). Significantly, a "ladder"-release pattern is obtained to balance maximal therapeutic efficacy and minimal dose frequency in the development of "pulsed" drug therapy.
Subject(s)
Bridged-Ring Compounds/chemistry , Imidazoles/chemistry , Nanoparticles/chemistry , Rotaxanes/chemistry , Silicon Dioxide/chemistry , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Molecular Structure , Nanopores , PhotolysisABSTRACT
OBJECTIVE: The main objectives of the study are to analyze fatal traffic-injury trends in 1987-2003 in Shanghai and predict its prevalence in near future and provide scientific data for the local governmental decision on developing practical working methods on traffic-injury prevention and control. METHODS: In this study, epidemiological method and Grey dynamic model GM (1,1) were introduced to analyze and forecast traffic-injury mortality rates respectively. RESULTS: There was an apparent increasing trend of traffic-related injuries in Shanghai from 1987 to 2003 with the rate of growth in motorization. The average rates of annual increase are 3.59% in fatalities (from 7.78 per 100,000 population to 14.18 per 100,000 population) during the period. Pedestrians were the most common type of victims (29.6%), followed by bicyclists (25.1%), and motorcyclists (24.1%). Males accounted for the majority of all victims, over 69%. The population of high-school and lower high-school education level represented 66.4% victims of total road-traffic injuries. And if no special factors effect its development, the traffic fatalities would be up to 17.84 per 100,000 population in 2010, when calculating from equations we found and validated Y(t) = 359.90 x e0.027(t-1)-352.13, (t = 1, 2, ..., N) for Shanghai. CONCLUSION: Our data indicate the risk of fatal traffic injuries has increased in recent years and will go on growing in the near future in Shanghai. The findings showed that Grey dynamic model GM (1,1) is eligible on the prediction and can be a tool for injuries forecasting, implementing effective policies, programs, and interventions for reducing traffic injuries in the big cities.
