Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome

Abstract

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.

Sinapine Thiocyanate Inhibits the Proliferation and Mobility of Pancreatic Cancer Cells by Up-Regulating GADD45A

“…ST, a quaternary amine alkaloid in cruciferous plants, has been widely studied because of its various pharmacological effects. Previous studies have indicated that ST alleviates vascular endothelial dysfunction in hypertension by repressing the activation of the NLRP3 inflammasome [13] and protects against a prothrombotic state leading to inflammatory damage [22]. Some studies have suggested that ST can be used as an effective natural compound for inhibiting the proliferation of Caco-2 cells through downregulation of P-glycoprotein [23].…”

“…ST has various pharmacological effects such as anti-inflammatory [10], antioxidant [11], and anti-angiogenic effects [12]. Liu et al revealed that ST protects vascular endothelial function and alleviates vascular endothelial cell injury in patients with spontaneous hypertension by repressing NLR family pyrin domain containing 3 inflammasome activation and reducing the expression of inflammatory mediators [13]. However, the effects and mechanisms of ST in PC have not been clarified.…”

NLRP3 inflammasome: The rising star in cardiovascular diseases

“…Moreover, vascular remodeling and vascular endothelial cell dysfunction are also pathogenesis resulting from hypertension, which can aggravate the development of hypertension in turn, leading to a vicious circle of elevating blood pressure pathologically. Blocking NLRP3 with sinapine thiocyanate or knocking down upstream receptor TLR4 posed a relief of endothelial dysfunction or vascular smooth muscle cell proliferation respectively ( 92 , 93 ).…”

Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3

“…This suggests that metformin can also inhibit NLRP3 inflammasome-mediated macrophage recruitment in atherosclerotic lesions in diabetic mice. Research shows that vascular normalization is linked positively with hampered NLRP3 inflammasome activation (109). Metformin has significant vascular protection, mainly through down-regulation of HIF1a and regulation of PDGF-B, thus promoting the normalization of dysfunctional vessels (110)(111)(112)(113)(114).…”