Editing MicroRNA (section)

====Mechanism====
MiR-712 targets tissue inhibitor of [[Metalloproteinase|metalloproteinases 3]] (TIMP3).<ref name="Son_2013" /> TIMPs normally regulate activity of matrix metalloproteinases (MMPs) which degrade the extracellular matrix (ECM). Arterial ECM is mainly composed of [[collagen]] and [[elastin]] fibers, providing the structural support and recoil properties of arteries.<ref name=":1">{{cite journal | vauthors = Basu R, Fan D, Kandalam V, Lee J, Das SK, Wang X, Baldwin TA, Oudit GY, Kassiri Z | title = Loss of Timp3 gene leads to abdominal aortic aneurysm formation in response to angiotensin II | journal = The Journal of Biological Chemistry | volume = 287 | issue = 53 | pages = 44083–96 | date = December 2012 | pmid = 23144462 | pmc = 3531724 | doi = 10.1074/jbc.M112.425652 | doi-access = free }}</ref> These fibers play a critical role in regulation of vascular inflammation and permeability, which are important in the development of atherosclerosis.<ref>{{cite journal | vauthors = Libby P | title = Inflammation in atherosclerosis | journal = Nature | volume = 420 | issue = 6917 | pages = 868–74 | year = 2002 | pmid = 12490960 | doi = 10.1038/nature01323 | bibcode = 2002Natur.420..868L | s2cid = 407449 }}</ref> Expressed by endothelial cells, TIMP3 is the only ECM-bound TIMP.<ref name=":1" /> A decrease in TIMP3 expression results in an increase of ECM degradation in the presence of d-flow. Consistent with these findings, inhibition of pre-miR712 increases expression of TIMP3 in cells, even when exposed to turbulent flow.<ref name="Son_2013" />

TIMP3 also decreases the expression of TNFα (a pro-inflammatory regulator) during turbulent flow.<ref name="Son_2013" /> Activity of TNFα in turbulent flow was measured by the expression of TNFα-converting enzyme (TACE) in blood. TNFα decreased if miR-712 was inhibited or TIMP3 overexpressed,<ref name="Son_2013" /> suggesting that miR-712 and TIMP3 regulate TACE activity in turbulent flow conditions.

Anti-miR-712 effectively suppresses d-flow-induced miR-712 expression and increases TIMP3 expression.<ref name="Son_2013" /> Anti-miR-712 also inhibits vascular hyperpermeability, thereby significantly reducing atherosclerosis lesion development and immune cell infiltration.<ref name="Son_2013" />