Macrophage Polarization as a Novel Therapeutic Target for Endovascular Intervention in Peripheral Artery Disease

Tan, Richard P.; Ryder, Isabelle; Yang, Nianji; Lam, Yuen Ting; Santos, Miguel; Michael, Praveesuda L.; Robinson, David; Ng, M.; Wise, Steven G.

doi:10.1016/j.jacbts.2021.04.008

Cited by 21 publications

(18 citation statements)

References 55 publications

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“…Nevertheless, given that we mainly focused on the effect of miR-21 on angiogenesis in responses to hypoxia, the involvement of arteriogenesis in this study requires further investigations. In addition to endothelial cells, vascular smooth muscle, myoblasts, and macrophage polarization should also be considered in the process of angiogenesis in PAD ( 45 , 46 ). Further studies will be required to investigate the effect of miR-21 on the recruitment, polarization and inflammatory phenotypes of macrophages and especially the crosstalk between cells, focusing on how it promotes angiogenesis.”…”

Section: Discussionmentioning

confidence: 99%

Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench

Chang

Lin

Huang

et al. 2022

Front. Cardiovasc. Med.

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With an increasing prevalence, peripheral arterial disease (PAD), cause by atherosclerosis is a new threat to public health beyond coronary artery disease and involves aberrant vascular endothelial cell proliferation and angiogenesis. The degree of vascular remodeling is influenced by the processes described. MicroRNA-21 (miR-21) has been found to play a critical role in cellular functions, including angiogenesis. Nevertheless, the effect of miR-21 on endothelial cells in response to hypoxia is largely unknown. Using wild-type C57BL/6J and miR-21–/– mice, we compared the capability of angiogenesis in response to hindlimb hypoxic/ischemia. In an in vitro study, we further studied whether overexpression of miR-21 mitigates hypoxia-induced apoptosis and impaired angiogenesis. Also, we prospectively collected the sera of patients with limb ischemia and followed the clinical information, including major adverse limb events (MALEs). Using laser Doppler perfusion imaging and CD31 staining, compared with miR-21–/– mice, wild-type mice expressed a significantly higher capability of angiogenesis and less apoptosis following 28 days of hindlimb hypoxic/ischemic surgery. In our in vitro study, after 24 h of hypoxia, proliferation, migration, and tube formation were significantly impaired in cells treated with the miR-21 inhibitor but rescued by the miR-21 mimic. Mechanistically, by suppressing PTEN/PI3K/AKT, miR-21 promoted angiogenesis and suppressed apoptosis in endothelial cells post hypoxia. In patients with limb ischemia, the high expression of circulating miR-21 was associated with less subsequent MALE. Collectively, miR-21 could be a biomarker associated with the endogenous ability of angiogenesis and reflect subsequent MALE in patients. Additionally, abolishing miR-21 impairs angiogenesis and promotes apoptosis post limb ischemia. Further studies are required to elucidate the clinical applications of miR-21.

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Section: Discussionmentioning

confidence: 99%

Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench

Chang

Lin

Huang

et al. 2022

Front. Cardiovasc. Med.

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“…Macrophage, especially its anti-inflammatory state (M2 phenotype), is crucial for angiogenesis, as it could induce wound healing by secreting profibrotic factors that contribute to tissue repair. However, damage-associated molecular signals released during the progression of PAD induce macrophages polarization into the pro-inflammatory state (M1 phenotype), further contributing to cellular damages 36 . PAD could also lead to fibrosis in red blood cells, the most abundant cells in the circulating blood, causing them to collide with the arterial wall, inducing local retention of lipid from the red blood cells membrane and local hemolysis.…”

Section: Peripheral Artery Diseasementioning

confidence: 99%

Therapeutic angiogenesis-based strategy for peripheral artery disease

Han¹,

Luo²,

Marcelina³

et al. 2022

Theranostics

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Peripheral artery disease (PAD) poses a great challenge to society, with a growing prevalence in the upcoming years. Patients in the severe stages of PAD are prone to amputation and death, leading to poor quality of life and a great socioeconomic burden. Furthermore, PAD is one of the major complications of diabetic patients, who have higher risk to develop critical limb ischemia, the most severe manifestation of PAD, and thus have a poor prognosis. Hence, there is an urgent need to develop an effective therapeutic strategy to treat this disease. Therapeutic angiogenesis has raised concerns for more than two decades as a potential strategy for treating PAD, especially in patients without option for surgery-based therapies. Since the discovery of gene-based therapy for therapeutic angiogenesis, several approaches have been developed, including cell-, protein-, and small molecule drug-based therapeutic strategies, some of which have progressed into the clinical trial phase. Despite its promising potential, efforts are still needed to improve the efficacy of this strategy, reduce its cost, and promote its worldwide application. In this review, we highlight the current progress of therapeutic angiogenesis and the issues that need to be overcome prior to its clinical application.

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“…Monocytes/macrophages play an important role in the pathophysiology of restenosis after angioplasty [3][4][5]17]. Currently, there is no consensus for the default endovascular therapy with all commercially available interventions.…”

Section: Using 19 F Mri To Identify Individuals At Riskmentioning

confidence: 99%

“…There are suboptimal long-term outcomes due to high rates of re-stenosis and a discussion about apparently higher rates of death in patients treated with DEB [18][19][20]. However, manipulation of the monocyte/macrophage response after angioplasty could beneficially modulate restenosis rates in limb revascularisation [4].…”

Section: Using 19 F Mri To Identify Individuals At Riskmentioning

confidence: 99%

“…Infiltration of macrophages into the vascular wall precedes neointimal growth and quantity is directly correlated to neointima area [3]. Therefore, targeting macrophage polarization and infiltration is an unmet goal to prevent restenosis after angioplasty in peripheral artery disease (PAD) [4]. Imaging of monocyte/macrophage infiltration after angioplasty might identify patients at increased risk for restenosis early after endovascular intervention [5].…”

Section: Introductionmentioning

confidence: 99%

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Quantitative assessment of angioplasty induced vascular inflammation with¹⁹F cardiovascular magnetic resonance imaging

Nienhaus

Walz

Rothe

et al. 2022

Preprint

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Early macrophage rich vascular inflammation is a key feature in the pathophysiology of restenosis after angioplasty.19F MRI with intravenously applied perfluorooctyl bromide-nanoemulsion (PFOB-NE) could offer ideal features for serial imaging of the inflammatory response after angioplasty. We aimed to non-invasively image monocyte/macrophage infiltration in response to angioplasty in pig carotid arteries using Fluorine-19 magnetic resonance imaging (19F MRI) to assess early inflammatory response to mechanical injury. Early macrophage rich vascular inflammation is a key feature in the pathophysiology of restenosis after angioplasty.19F MRI with intravenously applied perfluorooctyl bromide-nanoemulsion (PFOB-NE) could offer ideal features for serial imaging of the inflammatory response after angioplasty. In eight minipigs, injury of the right carotid artery was induced by either balloon oversize angioplasty only (BA, n=4) or in combination with endothelial denudation (BA + ECDN, n=4). PFOB-NE was administered intravenously three days after injury followed by1H and19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using immunohistology. Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and adventitial infiltration of monocytes/macrophages.19F signal could be detectedin vivoin four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8.Ex vivoanalysis revealed a linear correlation of19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was as about 400 cells/mm2. Therefore,19F MRI enables quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This might open an avenue to non-invasively monitor inflammatory response to mechanical injury after angioplasty and thus to identify individuals with distinct patterns of vascular inflammation promoting restenosis.One Sentence Summary19F MRI enables radiation-free quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity.

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Macrophage Polarization as a Novel Therapeutic Target for Endovascular Intervention in Peripheral Artery Disease

Cited by 21 publications

References 55 publications

Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench

Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench

Therapeutic angiogenesis-based strategy for peripheral artery disease

Quantitative assessment of angioplasty induced vascular inflammation with¹⁹F cardiovascular magnetic resonance imaging

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Macrophage Polarization as a Novel Therapeutic Target for Endovascular Intervention in Peripheral Artery Disease

Cited by 21 publications

References 55 publications

Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench

Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench

Therapeutic angiogenesis-based strategy for peripheral artery disease

Quantitative assessment of angioplasty induced vascular inflammation with19F cardiovascular magnetic resonance imaging

Contact Info

Product

Resources

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Quantitative assessment of angioplasty induced vascular inflammation with¹⁹F cardiovascular magnetic resonance imaging