New-Generation Drug-Eluting Stents for Patients With Myocardial Infarction

Cassese, Salvatore; Kastrati, Adnan

doi:10.1001/2012.jama.10465

Cited by 6 publications

(5 citation statements)

References 22 publications

(19 reference statements)

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“…Furthermore, previous studies specifically evaluating the role of p27 overexpression in a rat carotid model of balloon angioplasty, like the one used here, demonstrated that the upregulation of p27 led to VSMC growth arrest and attenuated neointimal lesion formation (36). Several reports have also demonstrated that sirolimus, clinically used in DES coating (1,11,14), blocks the degradation of p27, thereby preventing VSMC proliferation and migration (5,8). In particular, sirolimus treatment produces an increase in p27 by reducing p27-targeted degradation by phosphorylation at Thr187 (5,8).…”

Section: Discussionmentioning

confidence: 51%

“…However, all drugs currently approved to coat DES do not discriminate between proliferating VSMCs and endothelial cells (ECs), thus delaying reendothelialization and subsequent vascular healing (11)(12)(13)(14)(15). This lack of drug specificity has greatly increased the risk of neoatherosclerosis and late thrombosis, potentially catastrophic events primarily caused by incomplete endothelial coverage of the treated vessel (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

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A selective microRNA-based strategy inhibits restenosis while preserving endothelial function

Santulli¹,

Wronska²,

Uryu³

et al. 2014

J. Clin. Invest.

163

162

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Drugs currently approved to coat stents used in percutaneous coronary interventions do not discriminate between proliferating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). This lack of discrimination delays reendothelialization and vascular healing, increasing the risk of late thrombosis following angioplasty. We developed a microRNA-based (miRNA-based) approach to inhibit proliferative VSMCs, thus preventing restenosis, while selectively promoting reendothelialization and preserving EC function. We used an adenoviral (Ad) vector that encodes cyclin-dependent kinase inhibitor p27(Kip1) (p27) with target sequences for EC-specific miR-126-3p at the 3' end (Ad-p27-126TS). Exogenous p27 overexpression was evaluated in vitro and in a rat arterial balloon injury model following transduction with Ad-p27-126TS, Ad-p27 (without miR-126 target sequences), or Ad-GFP (control). In vitro, Ad-p27-126TS protected the ability of ECs to proliferate, migrate, and form networks. At 2 and 4 weeks after injury, Ad-p27-126TS-treated animals exhibited reduced restenosis, complete reendothelialization, reduced hypercoagulability, and restoration of the vasodilatory response to acetylcholine to levels comparable to those in uninjured vessels. By incorporating miR-126-3p target sequences to leverage endogenous EC-specific miR-126, we overexpressed exogenous p27 in VSMCs, while selectively inhibiting p27 overexpression in ECs. Our proof-of-principle study demonstrates the potential of using a miRNA-based strategy as a therapeutic approach to specifically inhibit vascular restenosis while preserving EC function.

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

A selective microRNA-based strategy inhibits restenosis while preserving endothelial function

Santulli¹,

Wronska²,

Uryu³

et al. 2014

J. Clin. Invest.

163

162

View full text Add to dashboard Cite

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“…The use of biodegradable polymers in newly-engineered DES offers the early protection against in-stent thrombosis avoiding its very late proinflammatory and prothrombotic effect 32,35 . Therefore, concerns regarding the late safety issue with DES are rather related to early-designed DES 8,36 . New DES replaced the early-generation DES in clinical practice, and what more, the old-fashioned sirolimus-eluting stents, i.e.…”

Section: Discussionmentioning

confidence: 99%

Drug-eluting stents compared to bare-metal stents improve short-term survival in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a nationwide prospective analysis of the AMIS Plus registry

et al. 2014

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“…4.1) are not able to differentiate EC from VSMC, T-cells or macrophages [227–229], and the inhibition of proliferation and migration affects all these cellular types [228, 230, 231], leading to an increased risk for late thrombosis, due to delayed/incomplete re-endothelization [204, 214, 232]. Thus, impaired endothelial coverage after angioplasty prolongs the window of vulnerability to thrombosis, requiring thereby a prolonged dual antiplatelet therapy.…”

Section: Angioplasty Stents and Mirsmentioning

confidence: 99%

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

Santulli

2015

Advances in Experimental Medicine and Biology

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Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are the main cell types within the vasculature. We describe here how microRNAs (miRs)—noncoding RNAs that can regulate gene expression via translational repression and/or post-transcriptional degradation—distinctively modulate EC and VSMC function in physiology and disease. In particular, the specific roles of miR-126 and miR-143/145, master regulators of EC and VSMC function, respectively, are deeply explored. We also describe the mechanistic role of miRs in the regulation of the pathophysiology of key cardiovascular processes including angiogenesis, atherosclerosis, and in-stent restenosis post-angioplasty. Drawbacks of currently available therapeutic options are discussed, pointing at the challenges and potential clinical opportunities provided by miR-based treatments.

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New-Generation Drug-Eluting Stents for Patients With Myocardial Infarction

Cited by 6 publications

References 22 publications

A selective microRNA-based strategy inhibits restenosis while preserving endothelial function

A selective microRNA-based strategy inhibits restenosis while preserving endothelial function

Drug-eluting stents compared to bare-metal stents improve short-term survival in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a nationwide prospective analysis of the AMIS Plus registry

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

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