Design of the lentivirus-driven sustained LR12 delivery system for TREM-1 inhibition for palliating atherosclerosis

Thankam, Finosh G.; Sanchez, David Jesse; Agrawal, Devendra K.

doi:10.1007/s11010-021-04321-z

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…LR12 is a specific inhibitor of TREM-1, and is a C-terminal amidation dodecapeptide (H-LQEEDTGEYGCV-CONH 2 ). 18 We judiciously opted for the cyclo dodecyl-based tag TAG-Rink-Fmoc ( 2f ) as the carboxy-terminal support for LR12 synthesis. On the one hand, due to its closed-loop alkyl system, tag 2f exhibited excellent solubility in the DCM or chloroform reaction medium.…”

Section: Resultsmentioning

confidence: 99%

One-pot and sustainable liquid-phase peptide extension for synthesis of C-terminal amidation peptides aided by small molecular tags

Li,

Jin,

Wang

et al. 2023

Org. Chem. Front.

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Section: Resultsmentioning

confidence: 99%

One-pot and sustainable liquid-phase peptide extension for synthesis of C-terminal amidation peptides aided by small molecular tags

Li,

Jin,

Wang

et al. 2023

Org. Chem. Front.

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“…Since both OSM and p27 kip1 regulate cell proliferation which in turn is associated with plaque vulnerability, we investigated the expression of p27 kip1 and OSM expression and their association with VSMC proliferation in hyperlipidemic microswine carotid arteries undergone angioplasty to induce atherosclerotic plaque and treated with or without TREM-1 inhibitor, LR12 [ 15 ]. An increased presence of inflammation, neointimal formation, medial thickening, and plaque formation in RAPAs treated with scrambled peptide compared to LR12-treated arteries in this study supports the potency of ox-LDL in inducing plaque formation and inflammatory cell recruitment and the beneficial effects of LR12 peptide in attenuating inflammation and plaque formation [ 15 , 17 , 18 ]. This difference may have been associated with the effects of LR12, which has previously been shown to dampen the pro-thrombogenesis effects of TREM-1 [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, suppression of p27 KIP1 has been associated with the suppression of smooth muscle cell proliferation and vascular remodeling in the pulmonary artery smooth muscle cells of mouse model [ 13 ] and in cultured cells [ 14 ]. This study was designed to investigate the expression of OSM and p27 KIP1 in carotid arteries with plaque and following treatment with anti-inflammatory agent LR12 inhibiting TREM-1 which is a mediator of inflammation and promoter of plaque vulnerability [ 5 , 15 ]. The association of OSM and p27 KIP1 expression with VSMC proliferation and plaque vulnerability was analyzed.…”

Section: Introductionmentioning

confidence: 99%

Targeting Oncostatin M Receptor to Attenuate Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine

Trinh,,

Shin,,

Rai,

et al. 2024

Cardiol Cardiovasc Med

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Atherosclerosis is a chronic inflammatory disease that leads to acute embolism via the formation of atherosclerotic plaques. Plaque formation is first induced by fatty deposition along the arterial intima. Inflammation, bacterial infection, and the released endotoxins can lead to dysfunction and phenotypic changes of vascular smooth muscle cells (VSMCs), advancing the plaque from stable to unstable form and prone to rupture. Stable plaques are characterized by increased VSMCs and less inflammation while vulnerable plaques develop due to chronic inflammation and less VSMCs. Oncostatin M (OSM), an inflammatory cytokine, plays a role in endothelial cells and VSMC proliferation. This effect of OSM could be modulated by p27 KIP1 , a cyclin-dependent kinase (CDK) inhibitor. However, the role of OSM in plaque vulnerability has not been investigated. To better understand the role of OSM and its downstream signaling including p27 KIP1 in plaque vulnerability, we characterized the previously collected carotid arteries from hyperlipidemic Yucatan microswine using hematoxylin and eosin stain, Movat Pentachrome stain, and gene and protein expression of OSM and p27 KIP1 using immunostaining and real-time polymerase chain reaction. OSM and p27 KIP1 expression in carotid arteries with angioplasty and treatment with either scrambled peptide or LR12, an inhibitor of triggering receptor expressed on myeloid cell (TREM)-1, were compared between the experimental groups and with contralateral carotid artery. The results of this study elucidated the presence of OSM and p27 KIP1 in carotid arteries with plaque and their association with arterial plaque and vulnerability. The findings suggest that targeting OSM and p27 KIP1 axis regulating VSMC proliferation may have therapeutic significance to stabilize plaque.

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“…LVs have the ability to integrate into the host genome and have been employed in various treatments. Some of the latest applications of LVs include the treatment of chronic granulomatous disease ( 87 ), sickle cell disease ( 88 ), Wiskott-Aldrich syndrome ( 89 ), atherosclerosis ( 90 ), severe combined immunodeficiency (SCID) ( 91 ), and human immunodeficiency virus (HIV) ( 92 ). Compared to other RVs such as gammaretrovirus, LVs have the advantage of being able to infect non-dividing cells, thanks to the presence of proteins with nuclear localization signals ( 93 ).…”

Section: Dna Delivery Systemsmentioning

confidence: 99%

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

Lu,

Lim,

et al. 2024

Front. Immunol.

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Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. The primary obstacle lies in the absence of an optimal delivery system, which significantly hampers the immunogenicity of DNA vaccines. We conduct a comprehensive analysis of the current status and limitations of DNA vaccines by focusing on both viral and non-viral DNA delivery systems, as they play crucial roles in the exploration of novel DNA vaccines. We provide an evaluation of their strengths and weaknesses based on our critical assessment. Additionally, the review summarizes the most recent advancements and breakthroughs in pre-clinical and clinical studies, highlighting the need for further clinical trials in this rapidly evolving field.

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Design of the lentivirus-driven sustained LR12 delivery system for TREM-1 inhibition for palliating atherosclerosis

Cited by 6 publications

References 27 publications

One-pot and sustainable liquid-phase peptide extension for synthesis of C-terminal amidation peptides aided by small molecular tags

One-pot and sustainable liquid-phase peptide extension for synthesis of C-terminal amidation peptides aided by small molecular tags

Targeting Oncostatin M Receptor to Attenuate Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

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