Zonulin reversibly modulate intestinal permeability (IP), the circulating zonulin levels were increased in diabetes, obesity, all of which are risk factors for atherosclerosis.
High mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) cause the activation of intracellular signaling, gene expression, and production of inflammatory cytokines and have been linked to many inflammatory disease states such as diabetes mellitus and atherosclerosis.
The present study indicated that miR‑92a prevented the migration of H2O2‑induced VSMCs by repressing the expression of SIRT1, and also provided a novel therapy to protect against the phenotypic change of VSMCs in atherosclerosis.
Angiotensin II and its type 1 receptor (AT1R) are both expressed in the adipose tissue and involved in the genesis of atherosclerosis as well as hypertension.
To further elucidate the role of COUP-TFII, we performed DNA microarrays in VEC transfected with the siRNA of COUP-TFII and subsequently stimulated with angiotensin II (AngII) and compared the expression profiles of 112 genes involved in various atherosclerosis-related pathways.
This is a model of hypertension and atherosclerosis because of high angiotensin II and aldosterone levels as a result of the transgenic expression of the entire human renin-angiotensin system.
Elevated levels of crosslinked AT1 receptor dimers on monocytes could sustain the process of atherogenesis, because inhibition of angiotensin II generation or of intracellular factor XIIIA activity suppressed the appearance of crosslinked AT1 receptors and symptoms of atherosclerosis in ApoE-deficient mice.
In the atherosclerosis mice, GQ-177 inhibited atherosclerotic lesion progression, increased plasma HDL and mRNA levels of PPARγ and ATP-binding cassette A1 in atherosclerotic lesions.
Together, these results indicate that the stimulation of SR-B1 expression in the liver is mediated in part by activation of the PPAR-gamma and RXR, and raise the possibility that this stimulation using thiazolidinediones conditions provides a protective mechanism for accelerated atherosclerosis in diabetes mellitus.
Although activation of PPARgamma appears to have beneficial effects on atherosclerosis and heart failure, it is still largely uncertain whether PPARgamma ligands prevent the development of cardiovascular diseases.
Our results establish a role for PPARgamma in the regulation of EC gene expression, with important implications for the clinical links between obesity and atherosclerosis.
Brachiocephalic arteries from TRAIL(-/-)ApoE(-/-) and ApoE(-/-) mice fed a high fat diet for 12 w demonstrated increased chondrocyte-like cells in atherosclerotic plaque, as well as increased aortic collagen II mRNA expression in TRAIL(-/-)ApoE(-/-) mice, with significant increases in calcification observed at 20 w. TRAIL(-/-)ApoE(-/-) aortas also had significantly elevated RANKL, BMP-2, IL-1β, and PPAR-γ expression at 12 w. Our data provides the first evidence that TRAIL deficiency results in accelerated cartilaginous metaplasia and calcification in atherosclerosis, and that TRAIL plays an important role in the regulation of RANKL and inflammatory markers mediating bone turn over in the vasculature.
Pharmacological activation of PPARgamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis.
<b>Results:</b> Our results indicated that the protein levels of HMGB1, TLR4, and pro-inflammatory cytokines including IL-1β, TNF-α were elevated with the development of atherosclerosis in CUMS mice, while the expressions of PPARγ, LXRα, and ABCA1 declined.
Notably, additional Tg(PPAR-γ) or pharmacological activation of PPAR-γ effectively prevented Tg(DNMT1)-induced proinflammatory cytokine production in macrophages and AS development in the mouse model.