**Acknowledgements**

targets for future vascular therapy. This information is important in targeting miRNAs aimed to decrease the level of abnormally expressed miRNAs and/or to increase miRNAs with

The recent demonstration that changes in expression of certain miRNAs in neointimal lesions, particularly upregulation of miRNA-21 and miRNA-221/-222 and downregulation of miRNA-145 support proliferative phenotype of VSMC suggests targeting miRNAs may represent a new form of therapy for vascular proliferative diseases [62, 64]. Furthermore, silencing of miRNA-21 and miRNA-221/222 by the local delivery of chemically engi‐ neered oligonucleotide-based miRNA inhibitors referred as "antigomirs" are efficient and specific silencers targeted for miRNA-21 and miRNA-221/222 was shown to reduce neointima formation [62, 64]. Similarly, use of an antagomir against miRNA -122, specifical‐ ly silenced miRNA-122 expression in the liver, lung, intestine, heart, skin and bone marrow for more than a week after one intravenous injection [82]. In another method, silencing of mir-145 or miRNA- 143 was achieved by adenovirus-mediated delivery of these miRNAs to vascular lesion, which appears to restore miRNA profile of vascular lesion that resem‐ bles normal tissue [66, 71]. Although these studies suggest that targeting miRNAs may represent a new therapy for vascular proliferative diseases, the miRNA-based technology

Exploring the microRNAome that controls VSMC phenotype and analysis of their targets have greater possibilities for unraveling unforeseen regulatory pathways and disease mechanisms, development of novel therapeutic approaches. miRNAs in cardiovascular research are a newly emerging powerful biomolecules, which demonstrate several unique opportunities for microRNAs-based therapeutics. Although some of the studies appear to indicate targeting certain miRNAs presents a potential therapy for atherosclerosis, knowledge of full scope of miRNAs in vascular pathogenesis is limited. With 1,000 or more microRNAs encoded by the human genome, only a few of which have been analyzed appear to be linked to vascular proliferative diseases. Considering the complexity of the multifactorial vascular proliferative diseases including atherosclerosis and restenosis, there may be several miRNAs and even several clusters of miRNAs, similar to miRNA-17-92 cluster, which impact the development of vascular pathogenesis. Therefore, several issues have to be addressed prior to use of miRNAbased technology can be translated to clinical therapy such as: profile of miRNAs responsible for vascular proliferative diseases needs to be determined; detailed effects of these miRNAs in the prevention and treatment of vascular proliferative diseases requires investigation; procedures for in vivo miRNA silencing needs to be improved to minimize off-target effects; technology for miRNA upregulation in arterial vessel wall requires development; and potential toxicity of miRNA-based therapy should be determined. Developing miRNAs into therapeutics reveals other significant challenges, such as methods of delivery and duration of action. Methods for local delivery to the arteries via catheters or coated stents may avert these challenges and should minimize off-target effects on other tissues. Besides their therapeutic

valuable functions in the intervention of occlusive vascular proliferative diseases.

is still long way from being translated to clinical therapy.

**16. Conclusion**

158 Current Trends in Atherogenesis

Our preliminary data presented in this article was made possible in part by research infra‐ structure support from grant numbers RR03045-21 and CO6 RR012537 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH)
