Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

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.

Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice.

BACKGROUND: Endothelial progenitor cells (EPCs) transplantation is one of the effective therapies for neointima associated with endothelial injury. Diabetes impairs the function of EPCs and cumbers neointima prevention of EPC transplantation with an ambiguous mechanism. Sodium Tanshinone IIA Sulfonate (STS) is an endothelium-protective drug but whether STS protects EPCs in diabetes is still unknown. METHODS: EPCs were treated with High Glucose (HG), STS, and Nucleotide-binding Domain-(NOD) like Receptor 3 (NLRP3), caspase-1, the Receptor of Advanced Glycation End products (AGEs) (RAGE) inhibitors, Thioredoxin-Interacting Protein (TXNIP) siRNA, and EPC proliferation, differentiation functions, and senescence were detected. The treated EPCs were transplanted into db/db mice with the wire-injured Common Carotid Artery (CCA), and the CD31 expression and neointima were detected in the CCA inner wall. RESULTS: We found that STS inhibited HG-induced expression of NLRP3, the production of active caspase-1 (p20) and mature IL-1ß, the expression of catalase (CAT) cleavage, γ-H2AX, and p21 in EPCs. STS restored the expression of Ki67, CD31 and von Willebrand Factor (vWF) in EPCs; AGEs were found in the HG-treated EPCs supernatant, and RAGE blocking inhibited the expression of TXNIP and the production of p20, which was mimicked by STS. STS recovered the expression of CD31 in the wire-injured CCA inner wall and the prevention of neointima in diabetic mice with EPCs transplantation. CONCLUSION: STS inhibits the aggravated neointima hyperplasia by protecting the proliferation and differentiation functions of EPC and inhibiting EPC senescence in diabetic mice. The mechanism is related to the preservation of CAT activity by inhibiting the RAGE-TXNIP-NLRP3 inflammasome pathway.

[The prevalence and risk factors of kidney disease in type 2 diabetic patients in rural Shanghai].

OBJECTIVE: To identify the prevalence and etiology of kidney disease and the related risk factors in type 2 diabetic patients in rural Shanghai. METHODS: A cross-sectional study in type 2 diabetic patients was conducted in a community of Shanghai. Questionnaire, clinical examination and laboratory tests were completed to collect the information about sociodemographic and healthcare characteristics. RESULTS: A total of 1421 eligible patients with complete information were screened from 1487 type 2 diabetic patients between November 2008 and March 2009. Of them, 40.75% were men, 59.25% were women, aged 37 - 86 (61.33 ± 9.65) years old, with diabetic duration of 0.25 - 43.92 (7.85 ± 6.34) years. Among them, 43.42% had diabetic retinopathy, 21.18% had neuropathy; 69.95% met the screening definition for hypertension, 76.07% for hyperlipidemia, 15.55% for hyperuricemia and 23.65% for cardiovascular disease. The control rates of fasting blood glucose, glycosylated hemoglobin, blood pressure and serum cholesterol were 57.71%, 33.99%, 14.22% and 2.46%, respectively. The prevalence of kidney disease, diabetic nephropathy and non-diabetic renal disease was 41.31%, 18.51% and 13.44%, respectively; and 9.36% were diagnosed as renal insufficiency of unknown reasons. Age, diabetic duration, hyperuricemia, diabetic retinopathy and poor control of blood pressure were independently associated with kidney disease; age and poor control of blood pressure were independently associated with diabetic nephropathy; age and hyperuricemia were independent risk factors of renal insufficiency in patients with diabetic nephropathy. CONCLUSIONS: Although the diabetic duration of these subjects is relatively short, the prevalence of complications including diabetic nephropathy is high. The high prevalence of non-diabetic renal disease shows the importance of further screening and diagnoses for prevention. Strict control of blood glucose, blood pressure, serum cholesterol and serum uric acid are key points of cutting down the prevalence of diabetic nephropathy and chronic kidney disease.