BACKGROUND Sirtuin1 (SIRT1) participates in a wide variety of cellular processes, but the molecular mechanism remains largely unknown. miR-155 is an element of the inflammatory signaling pathway in atherosclerosis.
Of relevance to this review is that inhibition of macrophage-specific miR-155 may be a viable therapeutic strategy to decrease inflammation associated with atherosclerosis.
This study demonstrates the characteristic impact of EVs from ox-LDL-treated and/or KLF2-transduced ECs on the monocyte/macrophage phenotype in vitro and in vivo.Q-PCR showed that both the atherosclerosis inducer ox-LDL and atheroprotective factor KLF2 regulated inflammation-associated microRNA-155 (miR-155) expression in human umbilical vein endothelial cells (HUVECs).
MiR-155 can inhibit the formation of atherosclerosis by interfering with the transformation of macrophages into foam cells that plays a critical role in the pathogenesis of atherosclerosis, but the precise mechanisms of miR-155 are still unknown.
Using apolipoprotein E knock-out (apoE<sup>-/-</sup>) mice on a high fat (HF) diet as an atherosclerotic obesity model, we demonstrated 1) microRNA-155 (miRNA-155, miR-155) is significantly up-regulated in the aortas of apoE<sup>-/-</sup> mice, and miR-155 deficiency in apoE<sup>-/-</sup> mice inhibits atherosclerosis; 2) apoE<sup>-/-</sup>/miR-155<sup>-/-</sup> (double knock-out (DKO)) mice show HF diet-induced obesity, adipocyte hypertrophy, and present with non-alcoholic fatty liver disease; 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin and increased expression of adipogenic transcription factors but lack glucose intolerance and insulin resistance.
MicroRNA-155 (miR-155), a multifunctional miRNA, plays an important role in many physiological and pathological conditions, including AS and autophagy.
In summary, increased miR-155 relieves chronic inflammation by a negative feedback loop and plays a protective role during atherosclerosis-associated foam cell formation by signaling through the miR-155-CARHSP1-TNF-α pathway.
We hypothesized that the A1166C polymorphism could correlate with different, ultra-sonographically defined plaque phenotypes, as well as with an altered expression of AT1R mRNA and protein in human carotid plaques (CP), and altered expression of miR-155 in patients with advanced atherosclerosis.
Contradictory results of microRNA-155 either promoting or preventing the pathophysiological process of atherosclerosis illustrate the complexity of this pleiotropic molecule.
For instance, miR-155 can exacerbate early stages of atherosclerosis by increasing the inflammatory activation and disturbing efficient lipid handling in macrophages.
The observation revealed that by enhancing STAT3 and NF-κB signaling and facilitating immune inflammation by targeting SOCS1, microRNA-155 plays a promotable role in atherosclerosis progression.
Thus, TNFα induced miR-155 may serve as a negative feedback regulator in endothelial inflammation involved in atherosclerosis by targeting nuclear transcription factor P65.
Our findings reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived foam cell formation during early atherogenesis and suggest that miR-155 is a potential therapeutic target for atherosclerosis.