MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Gareri, Clarice; Rosa, Salvatore De; Indolfi, Ciro

doi:10.1161/circresaha.115.308237

Cited by 108 publications

(92 citation statements)

References 164 publications

(217 reference statements)

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“…Interestingly, ACS patients undergoing percutaneous coronary intervention (PCI) saw their plasma concentration of platelet MPs decrease, leading the authors to conclude that platelet MPs may be both a promising biomarker for the development of ACS and a prognostic factor of PCI. A role for microRNAs in restenosis and thrombosis after vascular injury has also been proposed [80].…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

The clinical significance of platelet microparticle-associated microRNAs

Provost

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~ 9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.

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Section: Cardiovascular Diseasesmentioning

confidence: 99%

The clinical significance of platelet microparticle-associated microRNAs

Provost

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…To explore the role of AGGF1 in VSMCs functions, we studied neointimal formation, a process caused mostly by VSMCs proliferation and migration 19, 21, 24, 25, 26. Immunostaining showed that AGGF1 expression was dramatically reduced in carotid arteries with neointimal formation after vascular injury (Figure 1B and 1C).…”

Section: Resultsmentioning

confidence: 99%

“…Incidence of restenosis has been reduced to 17% to 41% with use of bare‐metal stents and further reduced to 10% with the use of drug‐eluting stents 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17. However, drug‐eluting stents presented with an unexpected problem of an increased rate of in‐stent thrombosis (0.5–3.1%),4, 5, 6, 7, 18, 19 which causes a significantly high 6.3% rate of MI and death 18, 20, 21, 22. This led to a 20% reduction in the use of drug‐eluting stents 23.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, despite important improvements in PTCA and placement of drug‐eluting stents to treat CAD and MI, restenosis continues to occur in about 10% of patients and in‐stent thrombosis poses a serious threat to patients. To resolve these issues, it is critical to identify new molecular targets for blocking restenosis and for use in drug‐eluting stents 19, 23…”

Section: Introductionmentioning

confidence: 99%

“…Restenosis is caused mainly by neointimal formation, which results from the proliferation and migration of vascular smooth muscle cells (VSMCs) 19, 21, 24, 25, 26. Therefore, genes and proteins involved in VSMCs functions become candidates for developing strategies for blocking restenosis.…”

Section: Introductionmentioning

confidence: 99%

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Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury

Yao

et al. 2017

JAHA

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BackgroundDespite recent improvements in angioplasty and placement of drug‐eluting stents in treatment of atherosclerosis, restenosis and in‐stent thrombosis impede treatment efficacy and cause numerous deaths. Research efforts are needed to identify new molecular targets for blocking restenosis. We aim to establish angiogenic factor AGGF1 (angiogenic factor with G patch and FHA domains 1) as a novel target for blocking neointimal formation and restenosis after vascular injury.Methods and Results AGGF1 shows strong expression in carotid arteries; however, its expression is markedly decreased in arteries after vascular injury. AGGF1+/− mice show increased neointimal formation accompanied with increased proliferation of vascular smooth muscle cells (VSMCs) in carotid arteries after vascular injury. Importantly, AGGF1 protein therapy blocks neointimal formation after vascular injury by inhibiting the proliferation and promoting phenotypic switching of VSMCs to the contractile phenotype in mice in vivo. In vitro, AGGF1 significantly inhibits VSMCs proliferation and decreases the cell numbers at the S phase. AGGF1 also blocks platelet‐derived growth factor‐BB–induced proliferation, migration of VSMCs, increases expression of cyclin D, and decreases expression of p21 and p27. AGGF1 inhibits phenotypic switching of VSMCs to the synthetic phenotype by countering the inhibitory effect of platelet‐derived growth factor‐BB on SRF expression and the formation of the myocardin/SRF/CArG‐box complex involved in activation of VSMCs markers. Finally, we show that AGGF1 inhibits platelet‐derived growth factor‐BB–induced phosphorylation of MEK1/2, ERK1/2, and Elk phosphorylation involved in the phenotypic switching of VSMCs, and that overexpression of Elk abolishes the effect of AGGF1.Conclusions AGGF1 protein therapy is effective in blocking neointimal formation after vascular injury by regulating a novel AGGF1‐MEK1/2‐ERK1/2‐Elk‐myocardin‐SRF/p27 signaling pathway.

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Endovascular Metal Devices for the Treatment of Cerebrovascular Diseases

Zhang

et al. 2018

Advanced Materials

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Cerebrovascular disease involves various medical disorders that obstruct brain blood vessels or deteriorate cerebral circulation, resulting in ischemic or hemorrhagic stroke. Platinum coils with or without biological modification have become routine embolization devices in the cerebral aneurysm sac to reduce the risk of bleeding. Many intracranial stents, flow diverters and stent retrievers have been invented with uniquely designed structures. To accelerate the translation of these devices into clinical usage, an indepth understanding of the mechanical and material performance of these metal-based devices is critical. However, considering the more distal location and tortuous anatomic characteristics of cerebral arteries, present devices still risk failing to arrive at target lesions. Consequently, more flexible endovascular devices and novel designs are under urgent demand to overcome the deficiencies of existing devices. Herein, we discuss the pros and cons of the current structural designs when these devices are applied to the treatment of diseases ranging broadly from hemorrhages to ischemic strokes, in order to encourage further development of such kind of devices and investigation of their use in the clinic. Moreover, novel biodegradable materials and drug elution techniques, and the design, safety and efficacy of personalized devices for further clinical applications in cerebral vasculature are discussed.

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MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Cited by 108 publications

References 164 publications

The clinical significance of platelet microparticle-associated microRNAs

The clinical significance of platelet microparticle-associated microRNAs

Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury

Endovascular Metal Devices for the Treatment of Cerebrovascular Diseases

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